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  • 2000-2004
  • 1980-1984  (21.408)
  • 1925-1929
  • 1900-1904  (1.503)
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  • 101
    Digitale Medien
    Digitale Medien
    Regulation of cerebello-cortical transmission in the rat ventromedial thalamic nucleus (1984)
    Springer
    Experimental brain research 55 (1984), S. 535-552 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Thalamus ; Cerebellum ; Basal ganglia ; Electrophysiology ; Rat ; Firing patterns ; Transmission
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary On the basis of antidromic stimulation we have identified two distinct neuronal populations in the rat ventromedial thalamic nucleus. The largest population (96%) are thalamo-cortical relay cells which project via the internal capsule to the cerebral cortex. The smaller population of cells (4%) project caudally to the reticular formation and superior colliculus. These two cell types could be distinguished further on the basis of their patterns of spontaneous discharge. Relay cells fluctuate between two activity patterns (i) a rhythmic pattern characterized by periods of high-frequency bursting, and (ii) a more tonic discharge pattern of single spikes. The caudally projecting cells had a characteristic fast, regular type of spontaneous firing. Brachium conjunctivum stimulation evokes two distinct responses in thalamic relay cells, (i) a short-latency single spike, (ii) a longer latency, rhythmic response of 2–3 spikes. Both excitatory responses are followed by a period of cell quiescence. The type of response is dependent upon the cell's firing pattern. The short-latency response occurs during tonic, single-spike activity whilst the longer latency response occurs during highfrequency bursting activity. The short-latency response can be altered to the long latency response by increasing the level of anaesthesia or by applying a conditioning shock to known inhibitory pathways. Conversely the long latency response can be altered to the short-latency response by decreasing anaesthesia or by stimulation of the reticular formation. It is argued that both response types are evoked monosynaptically by activation of the same cerebello-thalamic fibres but that different ionic conductances which are active at different levels of membrane polarization are responsible for the two response patterns. Efficient time-locked cerebellothalamo-cortical transmission occurs only during tonic single-spike activity, when cerebellar stimulation evokes a short-latency response. Such transmission is allowed or disallowed by the fine balance between converging excitatory and inhibitory afferents. In addition to a monosynaptic excitatory input from the cerebellar nuclei, relay cells received converging synaptic inputs from the substantia nigra, cerebral cortex, reticular formation and superior colliculus. Due to the anatomical arrangement in the rat it proved impossible to assess the role of the pallidum. The population of caudally projecting cells also received several converging synaptic inputs, but unlike those influencing relay cells, these inputs were all excitatory. We have obtained no clear physiological evidence for the occurrence of local interneurones within the ventromedial nucleus. However, a powerful recurrent inhibitory circuit is activated following antidromic activation of relay cells. The interneurones responsible for this inhibition appear to lie in the thalamic nucleus reticularis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00235285
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  • 102
    Digitale Medien
    Digitale Medien
    Evidence for a ventral septal projection to the hippocampal formation of the rat (1984)
    Springer
    Experimental brain research 55 (1984), S. 579-585 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Septo-Hippocampal projections ; Hippocampal afferents ; Cholinergic projections ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In a series of experiments in which the known projections of the septal complex to the hippocampal formation have been transected, we have used both anterograde and retrograde tracing techniques in an attempt to demonstrate a ventral septo-hippocampal pathway. In cases where transections of the fimbria, dorsal fornix and supracallosal stria were complete, injections of the retrograde tracers wheat germ agglutinin-conjugated horseradish peroxidase or Fast blue, resulted in labeled cells in the ipsilateral septal complex, primarily in the nucleus of the diagonal band. The number of cells labeled in these experiments was approximately 5–10% of that seen in experiments in animals with intact dorsal pathways who had received similar injections. The presence of a ventral pathway was confirmed in anterograde labeling experiments in which injections of 3H-amino acids were made into the septal complex. The autoradiogfaphs demonstrated that the projection terminates most heavily in the entorhinal cortex and to a lesser extent in the ventral subicular complex; there may be an additional minor projection to the temporal half of the hippocampus and dentate gyrus. Finally, using double labeling procedures, we were able to demonstrate that at least a portion of the cell population that gives rise to the ventral pathway demonstrates choline acetyltransferase immunoreactivity and is presumably cholinergic.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00235290
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  • 103
    Digitale Medien
    Digitale Medien
    The distribution of the projection from the parataenial nucleus of the thalamus to the nucleus accumbens in the rat: An autoradiographic study (1984)
    Springer
    Experimental brain research 54 (1984), S. 499-512 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Parataenial nucleus ; Nucleus accumbens ; Autoradiography ; Thalamus ; Limbic system ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In this study the intrastriatal distribution of afferents arising from the parataenial nucleus of the thalamus was investigated. Tritiated leucine and proline injected into the parataenial nucleus was found to densely label the entire anterior-posterior extent of the medial nucleus accumbens. The projection was for the most part limited to this striatal subregion, although some moderate labelling was found along the medial wall of the anterior caudateputamen. The terminal labelling within accumbens was characterized by a distinct patchiness. Other efferent connections of the parataenial nucleus observed in this study include the thalamic reticular nucleus, the basolateral and central nuclei of the amygdala, the septum, the medial frontal cortex, the entorhinal cortex and subiculum. This projection is distributed to the “limbic afferented” sector of striatum, and there is a nearly complete overlap between the parataenial afferents and those coming from hippocampus. The present findings suggest that the parataenial nucleus is an important thalamic link between limbic and striatal processing.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00235475
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  • 104
    Digitale Medien
    Digitale Medien
    The use of retrograde transport of horseradish peroxidase for studying the dendritic trees and axonal courses of particular groups of tract cells in the spinal cord (1984)
    Springer
    Experimental brain research 54 (1984), S. 529-537 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Cat ; Rat ; Spinal tract neurons ; Retrograde HRP transport ; Procedure and evaluation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Modifications have been made in Mesulam's method for labelling neurons by retrograde transport of horseradish peroxidase, with tetramethylbenzidine as chromogen, with the object of increasing the extent of labelling of dendrites and axons. A procedure was devised specifically for studying spinomedullary and medullospinal tract systems, involving implanting easily-made HRP-agar pellets into areas of controlled damage in particular spinal fascicles, and sealing the site of implant with cyanoacrylate glue. Lesions of other fascicles were often made to limit transport to the implanted fascicle. Fourth-order dendrites were regularly labelled over long (30 cm or more) transport distances: axons were also labelled over this whole distance, often allowing exact study of the initial course of particular axons. Controls in both cat and rat showed that the uptake of HRP under these circumstances occurred almost wholly from the region of axonal damage at the site of implant which can be characterized histologically.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00235478
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  • 105
    Digitale Medien
    Digitale Medien
    Is there a retinopetal system in the rat? (1984)
    Springer
    Experimental brain research 56 (1984), S. 502-508 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Visual system ; Retinopetal cells ; Lateral mesencephalic tegmentum ; Retrograde tracing ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The centrifugal innervation of the retina was reinvestigated in albino and pigmented rats with intraocular injections of horseradish peroxidase (HRP), radioactive wheat germ agglutinin (WGA) and proline. No labeled cells were found in the brains injected with HRP and proline, except some eye muscle motoneurons in one case apparently involving orbital contamination from the injection. In the cases injected with WGA and having a survival time of at least two days cells were labeled in the lateral mesencephalic tegmentum, ventral to the parabigeminal nucleus and in the periaqueductal gray. Both these findings are most likely due to transneuronal anterograde-retrograde transport of the tracer through the superior colliculus. The results yielded no compelling evidence for the existence of a direct retinopetal pathway in the rat, which is in contrast to a recently claimed retinal projection originating from the pretectum. Special attention was paid to the labeling in the lateral mesencephalic tegmentum, an area giving rise to retinal projections in various submammalian species. This finding is discussed with regard to the possibility that also in the rat the lateral tegmentum exerts an early influence on visual input, but at the “higher” collicular level and not at the “original” retinal one.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00237991
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  • 106
    Digitale Medien
    Digitale Medien
    Absence of reoxygenation damage in isolated heart cells after anoxic injury (1984)
    Springer
    Pflügers Archiv 401 (1984), S. 71-76 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Cardiac anoxia ; Enzyme release ; Reoxygenation damage ; Mitochondrial swelling ; Contracture development ; Cell lysis ; Adult heart cells ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Cultured adult cardiac myocytes were exposed to anoxia under substrate-free conditions and then reoxygenated. When comparing the oxygen deficient organ to the anoxic cell culture, we see that metabolic changes in the latter system proceed in a similar, yet prolonged manner, as in arrested hearts. Release of cytosolic enzymes starts with minor energetic disturbances and proceeds closely correlated to the actual ATP level. Below 2 μmol ATP/gww, an increasing number of cells becomes irreversibly damaged, above this level, 30 min reoxygenation leads to extensive recovery of the whole preparation. The results indicate that leakage of cytosolic enzymes during the early stage of anoxia is due to a gradual protein release from the individual cells and is related to reversible membrane alterations. Reoxygenation does not induce changes considered typical of the ‘oxygen paradox’. Since mechanical cell-cell interactions are absent in this model, it is suggested that aggravation of tissue damage in heart tissue reoxygenated late is mainly caused by mechanical forces.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00581535
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  • 107
    Digitale Medien
    Digitale Medien
    The effect of acute zimeldine and alaproclate administration on the acquisition of two-way active avoidance: Comparison with other antidepressant agents, test of selectivity and sub-chronic studies (1984)
    Springer
    Psychopharmacology 84 (1984), S. 188-195 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Zimeldine ; Alaproclate ; Antidepressants ; PCA ; Selectivity ; Subchronic administration ; Two-way ; One-way ; Avoidance ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The dose-dependent effect of acute zimeldine and alaproclate treatment upon the acquisition of two-way and one-way active avoidance in the rat was studied in a single-session and in a repeated-sessions design. Zimeldine (5–20 mg/kg, IP), but not alaproclate, caused disruptions of two-way avoidance acquisition. Acquisition deficits were also caused by citalopram and fluoxetine but not the other antidepressant drugs tested. Zimeldine, but not alaproclate or desipramine, caused a slight but non-significant impairment of one-way active avoidance; neither zimeldine nor alaproclate produced any effects upon fear conditioning and retention testing. The long-term action of p-chloroamphetamine (2×10 mg/kg) antagonised the acute zimeldine effect totally, and chronic treatment with zimeldine (15 days, 1×50 μmol/kg) and chlorimipramine (15 days, 2×10 μmol/kg) also caused some partial blockade of the two-way avoidance deficit. These data seem to suggest some involvement of serotonin (5-HT) in the observed disruptions of two-way active avoidance caused by acute zimeldine treatment.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427444
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  • 108
    Digitale Medien
    Digitale Medien
    Long-lasting tolerance to stimulatory effects of perinatal caffeine treatment (1984)
    Springer
    Psychopharmacology 84 (1984), S. 285-286 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Caffeine ; Tolerance ; Perinatal treatment ; Locomotor activity ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Pregnant rats were treated with caffeine in their drinking water at doses of 136.3 mg/kg/day during gestation and 222.2 mg/kg/day during lactation. The resulting off-spring at 60 days of age (40 days after drug withdrawal) were tested in an activity monitor cage. Spontaneous locomotor activity and that induced by caffeine (10, 30, 60 mg/kg/day) were observed. Treated rats showed apparent tolerance to caffeine-induced motility. Therefore perinatal caffeine treatment seems to induce long-lasting tolerance. This finding contrasts with those previously reported for chronic caffeine treatment in adult rats, where tolerance disappears after only 2–3 weeks following drug with-drawal.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427461
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  • 109
    Digitale Medien
    Digitale Medien
    Effect of naloxone administration upon responses of adrenal hormones to withdrawal from ethanol (1984)
    Springer
    Psychopharmacology 82 (1984), S. 181-184 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Corticosterone ; Adrenal catecholamine ; Ethanol ; Withdrawal ; Naloxone ; Stress ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats maintained on an ethanol-liquid diet developed physical dependence after 16 days. Activation of adrenocortical function and overactivity of the sympathoadrenal system were observed during withdrawal from ethanol. The opiate antagonist naloxone prevented the adrenomedullary response, and attenuated, though not significantly, the increases in serum corticosterone induced by ethanol deprivation. These findings suggest that endogenous opioid pathways may be involved in the ethanol-withdrawal syndrome.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427769
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  • 110
    Digitale Medien
    Digitale Medien
    Involvement of dopamine in the antinociceptive response to footshock (1984)
    Springer
    Psychopharmacology 82 (1984), S. 185-188 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Stress ; Antinociception ; Dopamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of drugs which alter dopaminergic function on footshock-induced antinociception were studied in the rat. Antinociception due to brief (30 s) footshock was inversely related to dopamine (DA). Thus, it was increased by the DA receptor antagonists pimozide and haloperidol and decreased by the specific D2 dopamine receptor agonist LY 141865, but not by the specific D1 agonist SKF 38393. Although pimozide increased the antinociceptive effect of 30-s shock, it decreased that of 30-min shock. It is suggested that DA may have physiological roles in stress-induced antinociception, and that these may differ according to the duration of stress.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427770
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  • 111
    Digitale Medien
    Digitale Medien
    Species differences in the relative analgesic potencies of some classical opiates and opioid peptides (1984)
    Springer
    Psychopharmacology 82 (1984), S. 400-402 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Opiates ; Opioid peptides ; Enkephalin analogues ; β-Endorphin ; Analgesia ; Species differences ; Morphine ; d-Met2, Pro5-enkephalinamide ; Rat ; Mouse ; Opiate receptors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The analgesic ED50 values of some classical morphine congeners (morphine, methadone, fentanyl, azidomorphine) in the rat and mouse tail-flick tests were found to be similar. However, several synthetic derivatives of the natural enkephalins were more potent in mice than in rats. (These analogs contain d-amino acid in position 2 and d- or l-sulfonic (or phosphonic) acid residue in position 5). β-Endorpin, d-Met2, Pro5-enkephalinamide and two partial agonists showed intermediate interspecies relative potencies. According to the data obtained, similar opiate receptors might mediate the analgesic action of classical opiates in rats and in mice. However, the opiate receptors responsible for the antinociceptive effects of the above mentioned enkephalin analogues must be dissimilar in the two species examined. The results are discussed in terms of the role of μ- and δ-receptors in mediation of the analgesic effect induced by different types of opioids.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427694
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  • 112
    Digitale Medien
    Digitale Medien
    Dopaminergic behaviour stereospecifically promoted by the D1 agonist R-SK & F 38393 and selectively blocked by the D1 antagonist SCH 23390 (1984)
    Springer
    Psychopharmacology 82 (1984), S. 409-410 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Dopamine D1 & D2 receptors ; SK & F 38393 ; SCH 23390 ; Grooming ; Behaviour ; Stereotypy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The selective D1 dopamine receptor agonist R-SK & F 38393 (20 mg/kg), but not its S-antipode, stereospecifically promoted episodes of prominent grooming behaviour. Typical stereotyped behaviour, such at that induced by apomorphine, was not seen. Grooming responses to 20 mg/kg R-SK & F 38393 were blocked by 0.1–0.5 mg/kg of the selective D1 antagonist SCH 23390 but not by 1.0–5.0 mg/kg of the selective D2 antagonist metoclopramide, while stereotyped behaviour induced by 0.5 mg/kg apomorphine was blocked by both antagonists. These results are consistent with certain individual dopaminergic behaviours such as grooming being mediated by D1 receptors. Other dopaminergic syndromes may involve complex functional interactions between D1 and D2 receptors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427697
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  • 113
    Digitale Medien
    Digitale Medien
    Biochemical effects and drug levels in rats after long-term treatment with the specific 5-HT-uptake inhibitor, citalopram (1984)
    Springer
    Psychopharmacology 83 (1984), S. 20-27 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Antidepressants ; Citalopram ; Long-term treatment ; Receptor binding ; Beta-receptors ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects in rats of long-term administration of the potent, specific 5-HT uptake inhibitor citalopram have been investigated. Citalopram hydrobromide (MW=405) was given in the diet, 99 or 25 μmol/kg daily, for 13 days or orally, 49 μmol/kg twice a day, for 14 days. High plasma and brain levels of citalopram were found during the treatment period, whereas negligible amounts were found 24 h after withdrawal. The 5-HT uptake mechanism in blood platelets was completely blocked, since levels of whole blood 5-HT during and shortly (2 days) after treatment were decreased by 75–90%. The drug load after the two highest doses in terms of plasma drug levels was the same as in depressed patients treated with citalopram. Receptor binding technique ex vivo was applied to different brain parts to measure receptor parameters for several neurotransmitters. All data were evaluated by Eadie-Hoffstee analysis. No changes were seen in B max and K d for β-receptors (3H-dihydroalprenolol) in frontal cortex, occipital+temporal cortex, whole cortex and limbic structures, 5-HT2 receptors (3H-spiroperidol) in frontal and whole cortex, α1-receptors (3H-prazosin) in “rest of brain” and DA D-2 receptors (3H-spiroperidol) in corpus striatum and limbic structures. The uptake mechanism for 5-HT as well as the inhibitory effect of citalopram on this uptake remained unaffected in brain synaptosomes derived from control and from citalopram (99 μmol/kg)-treated rats. Thus long-term treatment with citalopram does not induce changes in neurotransmitter receptors as seen with most tricyclic as well as newer “atypical” antidepressants. Most striking is the lack of β- and 5-HT2 receptor down-regulation. Since citalopram clinically shows clear antidepressant activity, this down-regulation does not seem to be a prerequisite of antidepressant activity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427416
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  • 114
    Digitale Medien
    Digitale Medien
    Antidepressant versus neuroleptic activities of sulpiride isomers on four animal models of depression (1984)
    Springer
    Psychopharmacology 83 (1984), S. 28-33 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Sulpiride isomers ; Imipramine ; Desipramine ; Haloperidol ; Apomorphine ; Hypomotility ; Hypothermia ; Behavioural despair ; Learned helplessness ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The atypical neuroleptic sulpiride is also prescribed for depression because of its activating effect. However, such an effect does not necessarily imply an action identical to that of classical antidepressants, and a laboratory comparison of the neuroleptic and antidepressant activities of sulpiride may contribute to a better definition of its psychotherapeutic profile. Sulpiride isomers were studied in the rat in four behavioural models of depression which are thought to be influenced by neuroleptics in different ways. Desipramine (imipramine) and haloperidol were employed in each test as a standard antidepressant and neuroleptic, respectively. The four tests were: 1) prevention of apomorphine-induced sedation: 2) antagonism of apomorphine-induced hypothermia; 3) behavioural despair (swim test); 4) learned helplessness (FR2 lever pressing escape). Desipramine ameliorated behaviour in all tests; haloperidol ameliorated the response to test 1, influenced that to test 2 in a neuroleptic-like way and worsened the responses to tests 3 and 4.(-)-Sulpiride worked in a similar way to haloperidol in all tests.(+)-Sulpiride significantly and dose-dependently ameliorated the responses to test 3 and was inactive in the others. No conclusion was drawn from test 1 owing to its lack of specificity; the results of the remaining tests indicated a neuroleptic profile of (-)-sulpiride and suggested a potential “antidepressant” activity of (+)-sulpiride which merits further investigation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427417
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  • 115
    Digitale Medien
    Digitale Medien
    Passive avoidance in rats: Disruption by dopamine applied to the nucleus accumbens (1984)
    Springer
    Psychopharmacology 83 (1984), S. 70-75 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Dopamine ; Locomotor activity ; Nucleus accumbens ; Passive avoidance ; State-dependent learning ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The acquisition of a one-trial step-through passive avoidance task was examined in rats following the administration of nialamide IP and dopamine (DA) or saline into the nucleus accumbens. DA-treated rats displayed impaired learning of the task as evidenced by their lower step-through latencies on a retest trial 7 days later. The specificity of this impairment was studied in a 2×2 design involving intracerebral injections prior to both training and testing trials. It was found that DA treatment prior to the training trial disrupted learning or memorization of the task but that DA did not affect performance or retrieval and did not induce state-dependent learning. These findings suggest that DA applied to the nucleus accumbens does not facilitate learning per se.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427425
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  • 116
    Digitale Medien
    Digitale Medien
    Central mediation of the conditioned taste aversion induced in rats by harmaline (1984)
    Springer
    Psychopharmacology 83 (1984), S. 384-389 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Intracerebral drug application ; Memory ; Neophobia ; Oliva inferior ; Saccharin preference ; Learning under anesthesia ; Cerebellar tremor ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The assumption that drugs used as unconditioned stimuli in conditioned taste aversion (CTA) studies act centrally was tested by comparing the effects of systemic and intracerebral injections of harmaline hydrochloride (H) in 340 rats. Intraperitoneal injection of 5–20 mg/kg but not of 2.5 mg/kg H administered 5 min after 15-min saccharin (0.1%) drinking decreased saccharin-water preference in a two-choice retention test, performed 48 h later, from 55% to 20%. Since CTA was not diminished when H (10 mg/kg) was injected into rats anesthetised immediately after saccharin drinking by pentobarbital (40 mg/kg), H (1.7–50 μg) was administered intracerebrally to anesthetised rats fixed in the stereotaxic apparatus. Injection of 3–6 μg H into the inferior olive elicited CTA comparable to that of systemic injection of 10 mg/kg H. Injections of 6 and 50 μg H into cerebellum and bulbar reticular formation elicited weaker CTA while neocortical, hypothalamic and mesencephalic applications were ineffective. CTA could also be elicited when 50 μg but not 6 μg H was injected into the inferior olive 1 or 2 h after saccharin drinking. This delay-dependent effect and failure of non-contingent H administration to change saccharin preference indicates that the H-induced CTA is not contaminated by a non-specific increase in neophobia. It is concluded that H probably elicits CTA by activation of caudal bulbar structures, including the nucleus of the solitary tract, area postrema and lateral reticular formation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00428552
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  • 117
    Digitale Medien
    Digitale Medien
    A study of the effects of clonidine on the EEG in rats treated with single and multiple doses of antidepressants (1984)
    Springer
    Psychopharmacology 84 (1984), S. 85-90 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Antidepressants ; Clonidine ; EEG activity ; Clonidine-antidepressants interaction ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The influence of repeated and single administrations of desipramine, amitryptiline, and mianserin on the EEG effects of clonidine has been investigated in rats implanted with chronic cortical electrodes. Clonidine induced a dose-dependent EEG synchronization in control animals. Signs of behavioral depression occurred after administration of moderate (0.1 mg/kg) and higher (0.2 mg/kg) doses of clonidine. Single doses of desipramine and amitryptiline attenuated the clonidine effect, while mianserine potentiated clonidine-induced synchronization. Antidepressants given once daily for 14 days completely (desipramine and amitryptiline) or partially (mianserin) reduced the effect of clonidine. Antidepressants alone produced only a slight effect on cortical EEG pattern.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00432031
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  • 118
    Digitale Medien
    Digitale Medien
    Effects of nicotine and d-amphetamine on intracranial self-stimulation in a shuttle box test in rats (1984)
    Springer
    Psychopharmacology 84 (1984), S. 109-114 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Intracranial self-stimulation ; Brain stimulation reward ; Shuttle box ; Nicotine ; d-Amphetamine ; Chronic administration ; Tolerance ; Motor performance ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats were permitted to turn on and off electrical stimulation of the medial forebrain bundle, by alternating between two photobeams running along opposite walls of a shuttle box. Entry into one beam (the “ON” beam) triggered the delivery of a succession of short, regularly occurring (1 Hz) pulse trains, which could be terminated by breaking the other (“OFF” beam). The two beams were frequently reversed. When this occurred, the rat was given a free period of 10 s in which to reorient, and brain stimulation reward was then assessed by the amount of time spent receiving brain stimulation (SST) within a fixed interval of time. SST increased with increasing current intensity. After training, subjects were tested for 10 consecutive days, alternately with saline and nicotine bitartrate (0.4 mg/kg SC base), and received a constant daily dose of the drug (0.4 mg/kg). Initially, nicotine visibly impaired motor performance for several minutes after injection, which may at least partly explain the observed reduction of SST; both effects waned across successive nicotine tests. Later in each 78 min session, nicotine consistently increased SST over a range of current, and drugged subjects entered the photobeams more frequently even when electrical stimulation was unavailable. d-Amphetamine sulphate (0.25, 0.75 mg/kg SC salt), given 15 min before testing, also increased SST and stimulated responding. The possible effects of motor impairment or activation on SST are discussed, and it is concluded that nicotine and d-amphetamine may have enhanced the rewarding properties of medial forebrain bundle stimulation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00432037
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  • 119
    Digitale Medien
    Digitale Medien
    Environmental experience produces qualitative changes in the stimulant effects of β-phenylethylamine in rats (1984)
    Springer
    Psychopharmacology 84 (1984), S. 132-135 
    Details
    ISSN: 1432-2072
    Schlagwort(e): β-Phenylethylamine ; Locomotor activity ; Rearing-stereotypy ; Environmental experience ; Amphetamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of β-phenylethylamine (PEA 6.25, 12.5, and 25.0 mg/kg IP) on spontaneous motor activity were examined in rats before (novel situation) and after (familiar situation) they had experience of the test environment, in an undrugged state. In a novel cage, 12.5 mg/kg PEA stimulated rearing and locomotion. A dose of 25.0 mg/kg PEA also increased rearing and produced stereotyped head movements, but did not increase locomotion, in a novel environment. In a familiar cage, both 12.5 and 25.0 mg/kg PEA stimulated locomotion and sniffing, whereas rearing was unaffected by PEA treatment under these conditions. These data provide a striking instance of a qualitative change in the behavioural response to a psychostimulant compound which is associated with the relative familiarity of the animal with the test environment. In addition, the results show that PEA induces stereotypy at high doses and increases locomotor activity at moderate doses, which is a further illustration of the similarity in the unconditioned behavioural effects of PEA and amphetamine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00432042
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  • 120
    Digitale Medien
    Digitale Medien
    Self-injection of diazepam in naive rats: Effects of dose, schedule and blockade of different receptors (1984)
    Springer
    Psychopharmacology 84 (1984), S. 174-177 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Schedule-induced self-injection ; Diazepam ; Benzodiazepine ; Ro 15-1788 ; Bicuculline ; Haloperidol ; Naloxone ; Dopamine ; GABA ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The present series of experiments had two main objectives: The first was to determine the conditions under which self-injection of the benzodiazepine diazepam would be optimal; the second was to identify neurochemical substrates which underlie the maintenance of diazepam selfadministration. Data from the first experiment indicated that rats maintained on an FI-1 (Fixed Interval of 1 min) schedule of food delivery self-injected significantly more diazepam than rats not maintained on this schedule. Results from the second experiment demonstrated that the benzodiazepine antagonist Ro 15-1788, and the GABA antagonist bicuculline, significantly reduced diazepam self-administration, but the opiate antagonist naloxone was without effect. Data from the third experiment showed that the dopamine antagonist haloperidol also significantly reduced the rate of diazepam self-injection. Thus, these findings indicate that the acquisition of diazepam self-injection occurs under an FI-1 schedule of food delivery, which has been shown to be middly stressful, while its maintenance depends upon the functional integrity of benzodiazepine and GABA receptors and upon the activity of deopaminergic pathways.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427442
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  • 121
    Digitale Medien
    Digitale Medien
    Restrained rats learn amphetamine-conditioned locomotion, but not place preference (1984)
    Springer
    Psychopharmacology 84 (1984), S. 163-166 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Place-preference ; Amphetamine ; Locomotor behavior ; Conditioned locomotion ; Hyperactivity ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The relationship between the motor-activating and positive-reinforcing properties of d-amphetamine was examined in the place-preference paradigm. Two groups of animals were trained to associate one environment with amphetamine, and another environment with saline. Annimals that were allowed to locomote in both environments during training later demonstrated a preference for the amphetamine-paired environment; animals in which hyperactivity was limited in both environments later failed to show any preference. However, both groups of animals demonstrated a conditioned locomotor activation to the amphetamine-associated environments. Our results suggest that a place-preference demonstrated for an amphetamine-paired environment depends on the ability of the drug to increase locomotor behavior.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427440
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  • 122
    Digitale Medien
    Digitale Medien
    Locomotor hyperactivity caused by dopamine infusion into the nucleus accumbens of rat brain: specificity of action (1984)
    Springer
    Psychopharmacology 82 (1984), S. 174-180 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Nucleus accumbens ; Intracerebral infusion ; Dopamine ; Neurotransmitter substances ; Locomotor activity ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats selected as high-activity and low-activity responders to the hyperactivity-inducing action of peripherally administered (-)N-n-propylnorapomorphine [(-)NPA] were subject to intra-accumbens infusion of dopamine, noradrenaline, serotonin, acetylcholine and GABA (0.48 μl/h, 25 μg/24 h, 13 days). Locomotor activity was measured during infusion and for a minimum of 35 days thereafter. After discontinuation of infusion the animals' responsiveness to (-)NPA was also assessed and, on the 2nd day of withdrawal, sensitivity to the hyperactivity-inducing action of acute intra-accumbens dopamine was determined. Dopamine caused a biphasic pattern of hyperactivity during infusion with peaks of responding between days 2–5 and 8–12: normal values returned after withdrawal of infusion. However, 2–3 weeks after withdrawal of intra-accumbens dopamine infusion animals showed reversed responding to (-)NPA challenge, the initial low-active animals giving a high-active response and high-active animals giving low-activity. Infusions of noradrenaline, serotonin, GABA and acetylcholine produced some increase in locomotor activity towards the termination of infusion, but no treatment could replicate the first hyperactivity peak and no treatment, after withdrawal, could reverse the responsiveness to (-)NPA of high- and low-active animals. Acute injections of dopamine into the nucleus accumbens showed that the infusion of the different neurotransmitter substances caused change within that nucleus. Nevertheless, changes in locomotor behaviour following the infusion of dopamine into the nucleus accumbens are specific for dopamine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00427768
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  • 123
    Digitale Medien
    Digitale Medien
    Assessment of drug metabolism in hepatic disease: Comparison of plasma kinetics of oral cyclobarbital and the intravenous aminopyrine breath test (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 95-101 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cyclobarbital ; aminopyrine ; liver disease ; 14CO2 breath test ; barbiturate ; pharmacokinetics ; hepatic drug metabolism ; cirrhosis ; alcoholic liver disease ; viral hepatitis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The exhalation of 14CO2 derived from an i.v. tracer dose of [dimethylamine-14C]aminopyrine has been investigated in normal controls and patients. They subsequently ingested 200 mg cyclobarbital calcium in the evening and the decline in the plasma drug level over the following 2 days was measured by thin-layer chromatography. The peak specific activity of exhaled 14CO2 occurred 0.5–2 h after 14C-aminopyrine injection in the absence of liver disease and in non-cirrhotic liver disorders. It was delayed in certain patients with cirrhosis. Compared to 8 medically healthy subjects, 10 patients with acute viral hepatitis, 8 with cirrhosis and 10 with fatty liver exhibited a significantly increased half-life of 14CO2 exhalation. Normal mean values were found in 12 patients with non-cirrhotic alcoholic liver disease and in 14 patients with non-hepatic diseases. The cyclobarbital (CB) half-life was prolonged and the clearance reduced in patients with viral hepatitis, cirrhosis, or alcoholic liver damage as compared to data from 17 control subjects. Due to a larger apparent volume of distribution, patients with fatty liver disease had an increased CB half-life, although its clearance was normal. A close negative correlation was detected between the clearance and the logarithm of the CB level measured 36 h after drug ingestion. The oral CB test evaluated from a single blood sample taken about 36 h after drug administration appears to be a useful indicator of human drug metabolising capacity. Discrimination between patients with and without disordered liver function was similar in the two drug elimination tests.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546715
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  • 124
    Digitale Medien
    Digitale Medien
    Nonlinear renal elimination kinetics of methotrexate due to saturation of renal tubular reabsorption (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 121-124 
    Details
    ISSN: 1432-1041
    Schlagwort(e): methotrexate ; psoriasis ; pharmacokinetics ; plasma levels ; urinary excretion ; renal clearance ; tubular absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentration and urinary excretion of methotrexate were followed in twelve psoriatic patients after intravenous and oral doses of methotrexate ranging from 7.5 to 30 mg. In six of the patients, a nonlinear relation was found between the fractional amount of methotrexate excreted in the urine and the corresponding area under the plasma concentration-time curve. The methotrexate clearance was found to be increased during the initial high plasma concentration, probably due to saturation of the tubular reabsorption of methotrexate. Considerable interindividual variation was found in the apparent saturation point of the active reabsorption, but up to 500–800 ng/ml first order kinetics still applied. At plasma concentrations below saturation, the renal clearance of methotrexate ranged from 52–102 ml/min (mean±SD, 83±19.4 ml/min).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546719
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  • 125
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of enprofylline in patients with impaired renal function after a single intravenous dose (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 87-93 
    Details
    ISSN: 1432-1041
    Schlagwort(e): enprofylline ; pharmacokinetics ; renal elimination ; renal insufficiency ; healthy subjects ; creatinine clearance ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Enprofylline, a new bronchodilating drug, was given i.v. at 1.0 mg/kg to 7 healthy subjects and to 14 patients with differing degrees of chronic renal insufficiency. Plasma and urine concentrations of unchanged drug were followed by HPLC. In the patients the plasma half-life was prolonged and the total and renal clearances were reduced in direct proportion to the degree of renal insufficiency as determined by creatinine clearance. The unbound fraction of enprofylline in plasma increased from 55% in the healthy subjects to 66% in the group of patients with the highest degree of renal impairment. The volume of distribution terms, Vβ and Vss, both tended to decrease with decreasing creatinine clearance. When the volume term calculations were based on the unbound drug level in plasma, this tendency was enhanced. Side-effects were noted in 4 subjects, and to some extent were related to the plasma level of the drug.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546714
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  • 126
    Digitale Medien
    Digitale Medien
    Comparative pharmacokinetics of sulphasalazine and sulphapyridine after rectal and oral administration to patients with ulcerative colitis (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 275-277 
    Details
    ISSN: 1432-1041
    Schlagwort(e): sulphapyridine ; sulphasalazine ; pharmacokinetics ; rectal administration ; oral administration ; plasma levels ; ulcerative colitis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Rectal administration of sulphasalazine to patients with ulcerative colitis has recently been shown to have similar therapeutic activity but fewer side effects than oral treatment. The present study is a comparison of the pharmacokinetics of sulphasalazine (SASP) and its metabolite sulphapyridine (SP) after rectal and oral administration of SASP to 6 patients with ulcerative colitis. The areas under the concentration-time curves (AUC) and the maximum concentrations (Cmax) of SASP and SP were significantly lower after rectal than oral administration of SASP (p〈0.05). These findings support the view that the lower frequency of side effects after rectal administration of SASP may result from the lower plasma levels of SASP and SP.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630300
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  • 127
    Digitale Medien
    Digitale Medien
    Relationship between the cardiovascular effects and steady-state kinetics of clonidine in hypertension (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 309-313 
    Details
    ISSN: 1432-1041
    Schlagwort(e): clonidine ; hypertension ; therapeutic window ; steady state concentration ; pharmacokinetics ; cardiovascular effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Clonidine was given orally as monotherapy in increasing daily doses from 3.1 to 25.7 µg/kg to patients with essential hypertension (n=6). When a steady state concentration in plasma was reached at each dose level, the blood pressure (BP) and heart rate were measured during a dosage interval. Effect time — plasma concentration data were submitted to nonlinear regression analysis, which showed that the observed BP effects could be dissociated into depressor and pressor components. A window for the antihypertensive effect was established. At a plasma clonidine concentration of 0.65±0.07 ng/ml 50% of the maximal depressor effect was found, and it was only separated by a factor of 2 from the half maximal pure pressor concentration in plasma. No relationship between the change in heart rate and the plasma clonidine was observed. The findings strengthen the importance of close monitoring of clonidine therapy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548760
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  • 128
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of midazolam in the aged (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 381-388 
    Details
    ISSN: 1432-1041
    Schlagwort(e): midazolam ; hypnotic drug ; benzodiazepine ; pharmacokinetics ; aged patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of midazolam, an imidazo-benzodiazepine derivative, have been studied in 13 subjects over the age of 60 years who received the drug intravenously (0.07 mg kg−1) as an induction agent for endoscopy. Two to three days later, 6 of these subjects received 5 mg of midazolam intramuscularly, and another 6 of the subjects received 10 mg of the drug orally. The plasma concentration-time curves were again studied pharmacokinetically. After intravenous dosing, the mean (± SD) elimination half-life (2.14±1.24 h) showed a statistically significant trend to increase with age in the subjects older than 60 years. While the mean (± SD) clearance value (0.30±0.19 l kg−1h−1) tended to fall with age in the elderly subjects, this trend was not statistically significant. Apparent volume of distribution did not appear to be related to advancing age beyond 60 years, and this parameter (mean ± SD) did not differ to a statistically significant extent between the aged subjects (0.77±0.47 l kg−1) and the young subjects studied previously (1.09±0.58 l kg−1). Atropine premedication did not appear to alter the dispositional parameters of the intravenously administered drug. Intramuscularly administered midazolam was absorbed rapidly. Bioavailability appeared incomplete (F=0.59±0.15, mean ± SD), possibly due to saturable elimination of the drug at the higher plasma levels which were obtained after intravenous midazolam. Oral bioavailability, relative to intravenous, was 0.34±0.17, (mean ± SD), with an appreciable but variable lag time (0.74±0.40 h, mean ± SD). Orally, in the dose used, the drug was an inefficient hypnotic with four of the six subjects failing to attain the plasma drug level of 44–50 µg l−1, which appeared to be the approximate threshold for sleep. It is impossible to know whether this failure represents an age related effect on drug absorption, or is a consequence of the upper alimentary tract abnormalities for which the endoscopies were done.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548771
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  • 129
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of cefoxitin administered by i.v. infusion to patients with a pleural effusion (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 389-392 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cefoxitin ; beta-lactam antibiotics ; pharmacokinetics ; serum concentration ; pleural fluid concentration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cefoxitin was studied in 6 healthy volunteers and in 5 patients with a pleural effusion after administration of a single dose of 30 mg/kg i.v. infusion. The serum and pleural fluid concentrations of cefoxitin were determined microbiologically. The elimination half-life of the antibiotic from pleural fluid in all cases was 2–3fold longer than from serum, which shows a difference between the kinetic elimination processes of the antibiotic from the two fluids. The slow elimination of cefoxitin from pleural fluid facilitates its accumulation in this compartment during a multiple dosage regimen.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548772
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  • 130
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of cefoperazone in patients undergoing chronic ambulatory peritoneal dialysis: Clinical and pathophysiological implications (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 609-612 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cefoperazone ; peritoneal dialysis ; pharmacokinetics ; terminal renal failure ; peritonitis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cefoperazone after i.p. and/or i.v. administration were studied in 12 CAPD patients. After i.v. injection, the plasma half-life was 2.65±0.4 h, the total clearance amounting to 70.1±19.2 ml/min. Peritoneal clearance was calculated to be 6.9±1 ml/min. After peritoneal instillation, the bioavailability was 63.9±5%. After repeated i.p. administration, no accumulation of the drug in the body was observed. Thus, cefoperazone can be safely administered for the treatment of peritonitis in CAPD patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543494
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  • 131
    Digitale Medien
    Digitale Medien
    Intra-individual consistency of prednisolone kinetics during long-term prednisone treatment (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 651-653 
    Details
    ISSN: 1432-1041
    Schlagwort(e): prednisolone ; prednisone treatment ; pharmacokinetics ; individual variation ; microsomal enzyme induction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eleven patients on long-term prednisone treatment were studied on two occasions separated by 45 to 325 days. In 10 patients the total body clearance of prednisolone only changed about 10%. In one case a 78.5% decrease was observed after stopping treatment with rifampicin and isoniazide. No association was found between the prednisone dose rate (mg/kg per month), patient age or mean endogenous plasma hydrocortisone level and prednisolone clearance/kg. The results indicate considerable intra-individual consistency of prednisolone kinetics if other conditions are not changed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543505
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  • 132
    Digitale Medien
    Digitale Medien
    D-propoxyphene kinetics in man: Significance of a deep third compartment (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 749-752 
    Details
    ISSN: 1432-1041
    Schlagwort(e): dextropropoxyphene ; pharmacokinetics ; half-life ; 3-compartment model ; steady state prediction ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Data from a previously published single dose study of d-propoxyphene 65 mg given i.v. to 8 healthy subjects have been subjected to non linear regression analysis by a curve-fitting program to test the applicability of a 2- and a 3-compartment open model. Analysis of residuals (difference between observed and computed concentrations) revealed similar systematic deviations in all 8 subjects when the 2-compartment model was used (5–10 h negative residuals, after 13 h positive residuals). In contrast, curve-fit by a 3-compartment model (with two parallel peripheral compartments) was good with no systematic deviations. The data show that a terminal monoexponential decline in d-propoxyphene concentrations cannot be expected until 15–30 h after single dose administration, and that the determination of the corresponding half-life is rather inaccurate. Accordingly, precise steady state level predictions may be difficult to obtain from conventional single dose studies with d-propoxyphene.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00541937
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  • 133
    Digitale Medien
    Digitale Medien
    Bioavailability and pharmacokinetics of phenytoin during pregnancy (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 105-110 
    Details
    ISSN: 1432-1041
    Schlagwort(e): phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02395215
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  • 134
    Digitale Medien
    Digitale Medien
    Clinical pharmacological studies with the vasodilator endralazine in patients with renal impairment (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 159-163 
    Details
    ISSN: 1432-1041
    Schlagwort(e): endralazine ; renal impairment ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of renal impairment on the pharmacokinetics of endralazine was studied in 12 patients; 4 patients on regular haemodialysis therapy (creatinine clearance less than 5 ml/min) and 8 patients with varying degrees of renal impairment (creatinine clearance 11–52 ml/min). Following an oral dose of 10 mg endralazine the mean terminal elimination half-life (βt1/2) in the dialysis sub-group was prolonged at 7.1 h (range 3.3 to 14 h), compared to 3.6 h in the other renal patients (and compared to 2.3 h in hypertensive patients with normal renal function). After one week's therapy with 10 mg B.D. endralazine in the 8 patients with moderate renal impairment there was a significant increase in βt1/2 to 8.6 h but there was no significant change in the area under the drug concentration-time curve and no evidence of drug accumulation. In this study those patients with the poorest renal function had the longest βt1/2 after acute dosing. There was a significant correlation between creatinine clearance and acute βt1/2 but there was considerable variability in individual patients and, even with severe degrees of renal impairment, major dose adjustments do not appear necessary.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544039
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  • 135
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of a fixed combination of sotalol and hydrochlorothiazide in hypertensive patients with moderate renal insufficiency (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 361-362 
    Details
    ISSN: 1432-1041
    Schlagwort(e): sotalol ; hydrochlorothiazide ; pharmacokinetics ; moderate renal failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Decreased elimination of a combined formulation of Sotalol (160 mg) and hydrochlorothiazide (25 mg) was found in patients with moderate renal insufficiency. Very slight accumulation of sotalol and hydrochlorothiazide was observed, so it appears unnecessary to reduce the dosage in patients with a creatinine clearance of 30 ml/min or more.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542176
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  • 136
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of propranolol during pregnancy (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 583-587 
    Details
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; pregnancy ; beta-adrenoceptor antagonist ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Propranolol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32 and 36 weeks gestation and when at least 6 weeks postparum. On both occasions, subjects were given propranolol 120 mg orally or 10 mg intravenously in randomised order with a minimum washout period of 1 week. Propranolol was assayed in plasma by gas-liquid chromatography with electron-capture detection and the pharmacokinetic parameters were investigated. There were no significant alterations in elimination half-life, clearance or apparent volume of distribution per kilogram antenatally compared with postnatally: bioavailability was also unchanged. It is concluded that the disposition of propranolol is not altered during pregnancy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00556896
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  • 137
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of the oral narcotic analgesic bezitramide and preliminary observations on its effect on experimentally induced pain (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 615-618 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Bezitramide ; oral absorption profile ; pharmacokinetics ; male volunteers ; experimental pain ; biliary excretion in rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The oral absorption of bezitramide 5 mg was studied in 7 human volunteers, using a specific radioimmuno-assay which measured both bezitramide and its active metabolite R-4618. A lag time of 0.5–1.0 h and a Cmax of 5.4 ng/ml plasma were found, the latter occurring 2.5–3.5 h after administration. The apparent elimination half-life varied from 11 to 24 h. Less than 0.3% of the dose was excreted unchanged in the urine. High concentrations in the faeces of some individuals indicate incomplete absorption and/or biliary secretion. The analgesic effect, using a standardized superficial electrical stimulation method, reached its maximum between 2.5 and 3.5 h after dosing, in accordance with the absorption phase. The duration of the effect was highly variable. Experiments in rats (n=6,3H-bezitramide 2.5 µg), demonstrated extensive biliary excretion (up to 70% of total radioactivity) and less than 3% of the label was removed by urinary excretion.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00556902
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  • 138
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of cimetidine in critically ill patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 341-346 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; pharmacokinetics ; critically ill patients ; intravenous administration ; dose individualization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Cimetidine disposition was studied after rapid (1 min) intravenous infusion in eight critically ill patients aged between 20 years and 77 years; one patient was studied on two occasions. Cimetidine dose was 300 mg in seven patients and 400 mg in the remaining patient. Arterial plasma cimetidine concentrations at the end of the infusion were very high and ranged from approximately 15–35 mg/l. Pharmacokinetic parameters displayed wide interpatient variability (coefficients of variation of 30–50%) and significant relationships emerged between some of these parameters and certain patient characteristics. Most notable, total systemic plasma clearance of cimetidine was directly related to estimated creatinine clearance (p〈0.01). This relationship might prove to be a useful method of individualizing cimetidine dosage in critically ill patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548765
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  • 139
    Digitale Medien
    Digitale Medien
    Effect of liver failure on the pharmacokinetics of cyclophosphamide (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 591-593 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cyclophosphamide ; liver failure ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cyclophosphamide was investigated in 7 patients in severe liver failure. The pharmacokinetic data were compared with those derived from a matched control group of patients with normal liver function. The half-life (t1/2) of cyclophosphamide following intravenous administration in patients with liver failure was 12.5±1.0 h (m±SD), which was significantly longer than in the normal controls in whom it was 7.6±1.4 h (p〈0.001). The mean total body clearance (Clt) was significantly smaller in liver failure at 44.8+8.6l·kg−1 than in the controls in whom it was 63.0±7.6l·kg−1 (p〈0.01). It is concluded that severe liver disease has a significant effect on the disposition of cyclophosphamide, and that it could lead to accumulation of the drug in the body.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543491
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  • 140
    Digitale Medien
    Digitale Medien
    Intrapatient variation in tobramycin kinetics in low birth weight infants during first postnatal week (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 647-649 
    Details
    ISSN: 1432-1041
    Schlagwort(e): tobramycin ; newborn infants ; intrapatient variations ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Nineteen newborn infants receiving tobramycin, 2.5 mg/kg every 12 h were studied on two occasions at steady-state during the first week of postnatal age. The two studies were separated by two to four days. Total body clearance of tobramycin averaged 1.15 and 1.14 ml/min/kg (p〉0.05), apparent volume of distribution averaged 0.82 and 0.68 l/kg (p〉0.05), and elimination half-life averaged 8.6 and 7.1 h (p〉0.05), during the first and second study, respectively. When the data were further analyzed based on the birth weight, tobramycin kinetics changed during the second study compared to the first study in very low birth weight infants. In eight infants ⩽1.5 kg birth weight, although total clearance of tobramycin was similar, the average apparent volume of distribution decreased from 1.04 l/kg during the first study to 0.73 l/kg during the second study (p〈0.05) and elimination half-life from 11.1 h during the first study to 8.7 h during the second study (p〈0.05). These data indicate that these infants may require a change in dosing interval with continued tobramycin therapy during the first week of postnatal age. Intrapatient variation in tobramycin kinetics should be considered, in addition to the interpatient variation reported previously, when monitoring the serum concentration to individualize tobramycin therapy in newborn infants ⩽1.5 kg birth weight.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543504
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  • 141
    Digitale Medien
    Digitale Medien
    Acetaminophen accumulation in pediatric patients after repeated therapeutic doses (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 57-59 
    Details
    ISSN: 1432-1041
    Schlagwort(e): acetaminophen ; pediatric patients ; fever therapy ; accumulation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Acetaminophen serum concentrations were studied in 21 infants and children with fever. The maximum serum concentrations ranged from 9.96 to 19.6 µg/ml after a single dose of 12–14 mg/kg and 13.9 to 40.1 µg/ml after a single dose of 22–27 mg/kg. Ten patients were restudied at steadystate after repeat doses had been given every 4 or 8 h for 1 to 3 days. Total area under the acetaminophen serum concentration-time curve normalized for dose averaged 0.181 (ml/min/kg)−1 after the first dose and 0.202 (ml/min/kg)−1 at steady-state (p〈0.05). Five patients showed a 13 to 44% increase in the AUC; one had a 10% decrease in the AUC; and four had less than 6% change in the AUC. There was no evidence of hepatotoxicity. These data suggest that acetaminophen may accumulate after repeated therapeutic doses in children with fever.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02395207
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  • 142
    Digitale Medien
    Digitale Medien
    Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 111-114 
    Details
    ISSN: 1432-1041
    Schlagwort(e): chlorambucil ; chronic lymphocytic leukaemia ; phenylacetic acid mustard ; food intake ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4–7.1) under fasting and 3.3 (range 1.3–7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00553164
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  • 143
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of the selective benzodiazepine antagonist Ro 15-1788 in man (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 115-117 
    Details
    ISSN: 1432-1041
    Schlagwort(e): benzodiazepine antagonist ; Ro 15-1788 ; healthy volunteers ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of the selective benzodiazepine antagonist Ro 15-1788 has been studied in 6 healthy male volunteers following a single intravenous dose of 2.5 mg. The drug was only slightly bound to plasma proteins (40±8%, mean±SD). A negligible amount (〈0.2% of the dose) of unchanged drug was recovered in urine. Hepatic elimination was rapid, as shown by a short t1/2 of 0.9±0.2 h, and high total plasma and blood clearances of 691±216 ml/min and 716±199 ml/min, respectively. The fast decline of plasma levels from about 60 to 2 ng/ml accounts for the short-lasting reversal of benzodiazepine-induced sedation by Ro 15-1788.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00553165
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  • 144
    Digitale Medien
    Digitale Medien
    Absorption of enprofylline from the gastrointestinal tract in healthy subjects (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 329-333 
    Details
    ISSN: 1432-1041
    Schlagwort(e): enprofylline ; healthy subjects ; absorption ; pharmacokinetics ; oral- ; duodenal- ; colonic administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Enprofylline, a new potent bronchodilator xanthine drug, was given orally as an aqueous solution to 6 healthy subjects in single doses of 2, 4 and 6 mg/kg. The two lower doses produced plasma concentrations in the range 1–4 mg/l, i.e. in the assumed “therapeutic interval” according to previous animal studies. A high 24 h urine recovery of unchanged drug, with mean values for the three dose levels ranging from 85 to 91% of the given dose, indicated good absorption and little metabolism. The dose-corrected area under the plasma concentration-time curve rose with dose as the latter was increased from 2 to 6 mg/kg. This indicates that the elimination of enprofylline is capacity-limited at high doses. Double peaks in the plasma concentration-time curves at the higher dose levels suggested intermittent and delayed gastric emptying as a possible explanation. This hypothesis was confirmed by studies in 6 other healthy subjects, who received the drug solution by three different routes; by mouth, via a catheter in the duodenum, and rectally via a catheter in the colon. The corresponding time to peak values (mean±SEM) were 32.5±8.7, 13.3±2.5, and 157±23 min.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542170
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  • 145
    Digitale Medien
    Digitale Medien
    Pharmacokinetic study of the new sulfamethopyrazine-trimethoprim combination (kelfiprim) in renal insufficiency (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 345-348 
    Details
    ISSN: 1432-1041
    Schlagwort(e): kelfiprim ; trimethoprim combination ; sulfamethopyrazine combination ; pharmacokinetics ; renal insufficiency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The combination of trimethoprim (TMP) and sulfamethopyrazine (SMP) has been successfully used to treat chronic urinary tract infections. Since parenchymal involvement associated with renal insufficiency of varying degree is not infrequent in these patients, it was considered important to study the pharmacokinetics of TMP and SMP in a fixed dose combination. Four groups of patients were studied: 1) 4 patients with endogenous creatinine clearance (CLcR) between 80 and 40 ml/min; 2) 3 patients with CLcR between 40 and 10 ml/min; 3) 3 patients on chronic peritoneal dialysis (CAPD); and 4) 3 patients on haemodialysis. A single oral dose of 250 mg TMP and 200 mg SMP was given to each patient. Multiple samples were collected over 9 days and the following pharmacokinetic parameters were calculated: total area under the plasma level curve, slow disposition rate constant β and the corresponding t1/2β, plasma clearance and the apparent volume of distribution. The results show that the two moieties of the TMP-SMP combination behaved differently in uraemic patients as fas as elimination rate was concerned. TMP was eliminated more slowly both in patients with diminished renal function and in those subjected to haemo- or peritoneal dialysis. The reduction in the rate of elimination of TMP was significantly correlated with the degree of renal impairment. The elimination of SMP, however, was not significantly affected by the reduced renal function; indeed a tendency to increase was noted, at least in dialyzed patients. However, as in patients with mild renal insufficiency (CLcR〉40 ml/min) no substantial change in plasma clearance rate need be expected, the TMP-SMP combination could be given to them in the same dose schedule as in people with normal renal function.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542173
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  • 146
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of canrenone and metabolites after base hydrolysis following single and multiple dose oral administration of spironolactone (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 441-446 
    Details
    ISSN: 1432-1041
    Schlagwort(e): spironolactone ; canrenone ; metabolites ; pharmacokinetics ; single/multiple oral doses ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of canrenone and ‘total metabolites’ after base hydrolysis was studied in eight young volunteers following single and multiple dose oral administration of spironolactone. The plasma levels of canrenone and ‘total metabolites’ were fitted to a two-compartment open model with a first-order absorption process. From our eight normal subjects studied, the harmonic mean of the distributive half-life (t1/2α) of canrenone was found to be 1.66 h, and the harmonic mean of the terminal elimination half-life (t1/2β) to be 22.6 h. Harmonic means of the distributive and elimination half-lives of ‘total metabolites’ after base hydrolysis were 2.48 h and 28.8 h respectively. The accumulation ratio of canrenone was 2.53, whereas that of ‘total metabolites’ was 1.89. Despite the fact that spironolactone has been shown to induce hepatic metabolism of other drugs, no evidence of autoinduction was noted in the present study, as plasma levels of canrenone and ‘total metabolites’ were found to obey a linear two-compartment model with reproducible absorption and disposition after single and multiple doses.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00549592
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  • 147
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of mepindolol in patients with chronic renal failure (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 429-433 
    Details
    ISSN: 1432-1041
    Schlagwort(e): mepindolol ; renal failure ; haemodialysis ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five patients with a creatinine clearance of 14 to 37 ml/min/1.73 m2 were each given an oral dose of 10 mg of the beta-blocker mepindolol sulphate (Corindolan). In addition, two dialysis patients received the same dose either during hemodialysis or on a dialysis-free day. Plasma levels of mepindolol were measured by a sensitive, specific HPLC method. Mepindolol was rapidly absorbed in all the patients. The maximum plasma level of 35±8 ng/ml was reached after 1.4±0.5 h. The half-life of disposition was 4.0±1.5 h. The area under the plasma concentration-time curve was 237±84 ng × h/ml. The data obtained were no different from those found in normal healthy volunteers.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00549590
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  • 148
    Digitale Medien
    Digitale Medien
    Tolerance and pharmacokinetics of A515U, an acyclovir analogue, in healthy volunteers (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 471-475 
    Details
    ISSN: 1432-1041
    Schlagwort(e): acyclovir ; A515U ; 6-deoxyacyclovir ; pharmacokinetics ; prodrug ; antiviral chemotherapy ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A515U (6-deoxyacyclovir) is an analogue of acyclovir devoid of antiviral activity in vitro but which is well absorbed and undergoes conversion to acyclovir after oral administration to rats. The tolerance and pharmacokinetics of various doses of A515U have been studied in 8 healthy volunteers. Single oral doses of 25, 50, 100, 200 and 400 mg A515U and 400 mg acyclovir for comparison were administered to the volunteers at weekly intervals. Concentrations of the parent drug and acyclovir were determined in plasma and urine. The prodrug was well tolerated and did not cause adverse reactions or changes in haematological or biochemical variables. It was well absorbed and conversion to acyclovir was rapid and extensive at all doses. Plasma concentrations of acyclovir achieved with 50 mg A515U orally were comparable to and less variable than those produced by 400 mg acyclovir. A515U was rapidly cleared with a short plasma elimination half life of approximately 0.5 h. The attainment of high plasma concentrations of acyclovir by oral administration of a prodrug may represent an important advance in antiviral chemotherapy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00549597
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  • 149
    Digitale Medien
    Digitale Medien
    Biperiden effects and plasma levels in volunteers (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 619-621 
    Details
    ISSN: 1432-1041
    Schlagwort(e): biperiden ; pharmacokinetics ; pharmacodynamics ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of biperiden was studied and compared with pharmacodynamics (pupil size, accomodation, self-rating mood scale) in 6 healthy volunteers. A single-blind cross-over design was employed with placebo and biperiden (4 mg as commercially available tablets). After a lag time of 0.5 h, biperiden was rapidly absorbed with a half-life of 0.3 h, plasma peak levels of 5 ng/ml being reached after 1.5 h. Biperiden showed good tissue penetration (distribution half-life 0.6 h; ratio of total to central distribution volume 9.6), the terminal half-life time of plasma concentration was 18 h, and the oral clearance was 146 l/h. The pharmacodynamic maximum lagged behind the plasma peak concentration by 1 (self-rating) to 4 h (accommodation).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00556903
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  • 150
    Digitale Medien
    Digitale Medien
    Ultrastructural changes in rat Clara cells induced by a single dose of O,S,S-trimethyl phosphorodithioate (1984)
    Springer
    Archives of toxicology 56 (1984), S. 59-65 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Trialkylphosphorothioates ; Rat ; Lung ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The oral administration of an LD50 dose (25 mg/kg) of O,S,S-trimethyl phosphorodithioate to rats induced immediate, cholinergic symptoms. A delayed respiratory crisis followed, 3–4 days later, involving a pronounced increase in lung weight and extensive injury to the alveolar epithelium. This compound also induced the immediate liberation of secretory granules from the Clara cells. Minor changes in the surface appearance of these cells were also observed but no signs of injury were found in any cells of the bronchiolar epithelium. The complement of secretory granules was monitored, by the morphometric analysis of ultrathin sections. Clara cells from control animals were found to contain 9.55±1.16 (SEM) granules per cell profile. The Clara cells from dosed animals were largely devoid of granules until the 3rd day after administration. Many of these agranular cells were arranged in clusters and often showed signs of mitotic division. In surviving animals the subsequent replacement of granules resulted in a large increase in the numbers present and many exhibited abnormal morphology. Over twice the normal complement of granules, 22.45±0.42 (SEM) per cell profile, was found 6 days after dosing. The complement of granules subsequently returned to normal levels and the clusters of Clara cells were resolved within 14 days of dosing.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00316355
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  • 151
    Digitale Medien
    Digitale Medien
    Comparison between the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and six other compounds on the vitamin A storage, the UDP-glucuronosyltransferase and the aryl hydrocarbon hydroxylase activity in the rat liver (1984)
    Springer
    Archives of toxicology 55 (1984), S. 16-19 
    Details
    ISSN: 1432-0738
    Schlagwort(e): TCDD ; 2,3,7,8-Tetrachlorodibenzo-p-dioxin ; 3-Methylcholanthrene ; Phenobarbital ; 2,3,7,8-Tetrabromodibenzo-p-dioxin ; Toxaphene ; 5-Chloro-2-(2,4-dichlorophenoxy)phenol ; 4,5,6-Trichloro-2-(2,4-dichlorophenoxy)phenol ; Vitamin A ; Retinol ; UDP-glucuronosyltransferase ; Aryl hydrocarbon hydroxylase ; Liver ; Rat ; High pressure liquid chromatography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrabromodibenzo-p-dioxin (TBrDD), 5-chloro-2-(2,4-dichlorophenoxy)phenol(3-Cl-predioxin) 4,5,6-trichloro-2-(2,4-dichlorophenoxy)phenol (5-Cl-predioxin), toxaphene, 3-methylcholanthrene (3-MC) and phenobarbital (PB) on the vitamin A storage, UDP-glucuronosyltransferase (UDPGT) and aryl hydrocarbon hydroxylase (AHH) activities in the liver of Sprague-Dawley rats was investigated. Vitamin A was determined as retinol by high pressure liquid chromatography. UDPGT was measured with p-nitrophenol as an aglycone and AHH with 3,4-benzopyrene as a substrate. Both in TCDD- and toxaphene-treated animals a reduced body weight gain was recorded, but no other overt signs of toxicity were seen in this study. Both the concentration and the total amount of hepatic retinol was significantly reduced in TCDD-, 3-MC-, PB- and TBrDD-treated animals. These compounds were also those which gave the most significant enzyme induction as regards the UDPGT and AHH activities. However, the reduction of hepatic retinol caused by these compounds did not correlate with the enzyme activities studied. When compared on a molecular basis, TCDD and TBrDD were in the order of several magnitudes more potent as reducers of hepatic retinol and likewise as enzyme inducers.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00316580
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  • 152
    Digitale Medien
    Digitale Medien
    Ro 15-1570, a new sulfur-containing retinoid devoid of bone toxicity in rats (1984)
    Springer
    Archives of toxicology 56 (1984), S. 117-122 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Rat ; Retinoids ; Bone alterations ; Adverse effects ; Arotinoid ethylsulfone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Repeated ingestion of high doses of retinoids cause the so-called hypervitaminosis A syndrome. In rats the main symptoms are weight loss, alopecia, erythema, desquamation of the skin, and alterations of the skeletal system, including bone fractures. In the present study, three retinoids (Ro 15-1570, arotinoid ethylsulfone, 6 mg/kg; retinoic acid, 100 mg/kg and etretinate, 50 mg/kg) were administered orally to rats for 1 and 2 weeks, respectively, to six male and six female rats/group. All the above changes were induced by all three retinoids, with the exception that the arotinoid ethylsulfone Ro 15-1570 did not cause bone alterations. The absence of toxic effects on the bones by Ro 15-1570 was confirmed by X-ray-film examinations, densitometry of the X-rayed femora and tibiae, examination of the thickness of the femoral and tibial compacta in histological slides plus the determination of the femoral ash weight and its main inorganic constituents (calcium, magnesium, sodium, and potassium). The present demonstration that the arotinoid ethylsulfone Ro 15-1570 was devoid of bone toxicity constitutes major progress in the pharmacologic development of retinoids with a better balance between therapeutic and adverse effects.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00349083
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  • 153
    Digitale Medien
    Digitale Medien
    Glucuronidation in rat intestinal epithelial cells (1984)
    Springer
    Archives of toxicology 55 (1984), S. 123-126 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Rat ; Intestinal cells ; Glucuronidation ; 1-Naphthol ; Glucose ; Fructose ; d-Galactosamine ; Ethanol ; Diethyl ether ; Sorbitol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Glucuronidation of 1-naphthol was studied in mucosal cells isolated from the rat intestine. Glucuronidation was directly dependent on the supply of extracellular carbohydrates. Basal glucuronidation (ca. 0.3 nmoles/min · mg cell protein) was increased 2- to 3-fold by adding glucose or fructose to the incubation medium. Saturation of glucuroniation was achieved by adding 0.3 mM glucose, while saturation by fructose was not reached at concentrations below 2 mM. No carbohydrate reserves able to support glucuronidation appear to be present in intestinal cells, since no difference in glucuronidation was observed between cells prepared from fasted (18 or 42 h) and control rats. Glucuronidation was decreased by adding d-galactosamine to the incubation medium, but only when extracellular glucose was present. Various chemicals which are known to inhibit glucuronidation in hepatocytes (ethanol, diethyl ether, sorbitol) did not influence the glucuronidation of 1-naphthol in isolated intestinal cells. Only when ethanol was added to mucosal cells in the absence of extracellular glucose was a small decrease in glucuronidation observed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00346050
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  • 154
    Digitale Medien
    Digitale Medien
    Phthalate esters (1984)
    Springer
    Archives of toxicology 55 (1984), S. 132-136 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Phthalate esters ; Inhalation ; Rat ; Enzymatic activities
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Male Sprague Dawley rats were exposed to dibutylphthalate (DBP) by inhalation with concentrations of 0.5, 2.5, and 7.0 ppm in the air for 5 days. The concentrations were considered relevant to human exposure. No quantitative changes were observed in liver microsomal cytochrome P-450 related enzymes, but significant increase was observed in the liver microsomal metabolism of benzo(a)pyrene and n-hexane, in the 2.5 ppm and 0.5 ppm groups, respectively. Inhaled DBF decreased in a dose-dependent way the lung microsomal concentration of cytochrome P-450 by as much as 63%, which was reflected in a significant reduction of the microsomal metabolism of n-hexane and benzo(a)pyrene in the 7.0 ppm group. It is concluded that DBP in doses relevant to human air exposure influences the cytochrome P-450 enzyme system in both liver and lung, with lung as the main target organ. The observed effects in lung microsomes were similar to those earlier reported after IP administration of high doses of DBP.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00346052
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  • 155
    Digitale Medien
    Digitale Medien
    A method of studying the intestinal absorption of aluminium in the rat (1984)
    Springer
    Archives of toxicology 55 (1984), S. 168-172 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Aluminium ; Intestinal absorption ; Methodology ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Aluminium (Al) intoxication in dialysis patients is held to be caused not only by Al in the dialysis fluid but also by Al from orally administered phosphate binders. Studies on Al absorption in patients and healthy individuals as well as in animals are still scarce, and do not provide sufficient data to characterize the absorption process. This paper presents a method of studying the process of Al absorption in a perfusion system of rat small intestine in vivo, in combination with a cannulation system of the portal vein for serial blood sampling. Determination of concentrations of an absorbed substance in samples of both the perfusion medium and the portal blood, collected during the perfusion period, may clarify the nature of the absorption process. Although this method appears to be useful for the study of the intestinal absorption of any substance, it was adapted for the study of the intestinal absorption of Al compounds. The usefulness of this method for studying Al absorption was demonstrated in an experiment in which Al chloride (0.5 g/l) in buffered media of pH 7.0, 7.5, and 8.0 was perfused through the rat small intestine over a period of at least 30 min. The results of this experiment indicate that a decrease in pH of the perfusion medium leads to an increase in absorption of Al in the portal blood.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00316122
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  • 156
    Digitale Medien
    Digitale Medien
    The effect of 2,3-dimercaptopropane sodium sulfonate on mercury retention in rats in relation to age (1984)
    Springer
    Archives of toxicology 55 (1984), S. 250-252 
    Details
    ISSN: 1432-0738
    Schlagwort(e): 203Hg ; DMPS ; Age ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effectiveness of DMPS (sodium 2,3-dimercaptopropane-1-sulfonate) in reducing inorganic mercury retention was studied in 2-, 6-, and 28-week-old albino rats. 203Hg was administered IP. The chelating agent DMPS was administered by IP injection at a dose of 250 μmol/kg body weight three times, 1 day after 203Hg administration and at 24 h intervals thereafter. The whole body retention determined 1, 2, 3, and 6 days after 203Hg administration showed that DMPS decreased the body retention of mercury in all age groups, being about twice as effective in adult compared to suckling rats. The reduced effectiveness was due to the reduced efficacy of DMPS in reducing kidney retention in young animals. In other organs the effectiveness of DMPS was not age dependent. These and previous results obtained with different chelating agents and other metals indicate that age might be an important factor in chelation therapy in general.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00341020
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  • 157
    Digitale Medien
    Digitale Medien
    In vivo metabolism of dimethylformamide and relationship to toxicity in the male rat (1984)
    Springer
    Archives of toxicology 56 (1984), S. 87-91 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Dimethylformamide ; N-Hydroxymethyl-N-methylformamide ; N-Methylformamide ; Metabolism ; Toxicity ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract After in vivo administration of dimethylformamide (DMF) to male rats, about 50% of the dose is excreted in urine as N-hydroxymethyl-N-methylformamide (DMF-OH) and about 4% as N-methylformamide (NMF). NMF is not a product of DMF-OH biotransformation but is directly formed from DMF. Comparison of the acute toxicity of DMF, DMF-OH and NMF shows that NMF is more toxic than DMF-OH, which is itself more toxic than DMF. This study explains the different toxicity profile of DMF and NMF which until recently was believed to represent the main metabolite of DMF.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00349077
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  • 158
    Digitale Medien
    Digitale Medien
    The toxicity and neuropathology of 2,4,5-tribromoimidazole and its derivatives in rats (1984)
    Springer
    Archives of toxicology 56 (1984), S. 109-112 
    Details
    ISSN: 1432-0738
    Schlagwort(e): 2,4,5-Tribromoimidazole ; Rat ; Neuronal necrosis ; Uncoupling of oxidative phosphorylation ; Ataxia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract 2,4,5-tribromoimidazole and its 1-n-butylcarboxylate and 1-dimethylcarbamoyl derivatives, when administered to rats, induced poisoning typical of uncouplers of oxidative phosphorylation. At 48 h rats surviving a single toxic dose of 20–60 mg/kg developed permanent incoordination of the hindlimbs in the absence of brain oedema. Neuropathologic examination of brain and spinal cord from perfused fixed rats at 24 h revealed neuronal necrosis and chromatolysis in the vestibular nucleus, the outer parietal neocortex and red nucleus. Chromatolysis and necrosis in these areas had increased at 72–96 h and were also observed in the deeper layers of the neocortex, the medial entorhinal cortex, the reticular formation, the grey matter of the spinal cord extending into the ventral horns, the dorsal, and ventral cochlear nuclei and the deep cerebellar nuclei, in decreasing order of severity. Neuronal necrosis was accompanied by an increased glial response, including neuronophagia and at 16 days with astroglial hypertrophy and hyperplasia.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00349081
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  • 159
    Digitale Medien
    Digitale Medien
    Differences in the distribution of methyl mercury in erythrocytes, plasma, and brain of Japanese quails and rats after a single oral dose (1984)
    Springer
    Archives of toxicology 56 (1984), S. 132-135 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Methyl mercury ; Toxicokinetics ; Differential toxicity ; Japanese quail ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Distribution of a single oral dose of methyl mercury (10 mg Hg/kg body weight) was followed from 90 min up to 120 h in plasma, erythrocytes, and brain of Japanese quails and rats. Significantly higher Hg concentrations were observed in plasma and brain of quails and red blood cells of rats. Blood/brain ratio decreased in quails from 6 to 2 at 24 h and 120 h respectively, whereas it increased in rats. Erythrocyte/plasma ratio in quails was about three times lower and averaged 54. The differences in Hg distribution were accompanied by a more than 3-fold higher acute toxicity in quails under adequate experimental conditions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00349086
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  • 160
    Digitale Medien
    Digitale Medien
    Pharmacokinetic and pharmacodynamic interaction study of diazepam and metoprolol (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 223-226 
    Details
    ISSN: 1432-1041
    Schlagwort(e): diazepam ; metoprolol ; drug combination ; pharmacodynamics ; pharmacokinetics ; drug metabolism ; sedation ; interaction study
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 6 normotensive, healthy male volunteers the pharmacodynamic responses (blood pressure, heart rate; sedation index, tracking test, reaction time) to metoprolol (100 mg bid orally), diazepam (0.1 mg/kg intravenously) and to their combination were studied. The pharmacokinetics of diazepam were also compared in a cross-over experiment, with and without pretreatment by the β-adrenoceptor antagonist to evaluate the possibility of a drug interaction. The pharmacodynamic and pharmacokinetic investigations indicated that metoprolol only slightly impaired the elimination of diazepam (18% decrease in total clearance, 25% increase in elimination half-life). The pharmacodynamics of metoprolol (17% decrease in heart rate, 17% decrease in diastolic RR) was not significantly altered by the bolus injection of diazepam. The extent of prolongation in choice reaction time (RT2) induced by diazepam was significantly (p=0.001) more pronounced following the co-administration of metoprolol. However, the results of RT1, the tracking test and the sedation index did not indicate any increased effect due to the β-blocking agent. It is concluded that concomitant treatment with metoprolol and diazepam causes only minor and clinically irrelevant changes in drug metabolism and drug response.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630289
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  • 161
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of estramustine phosphate (Estracyt®) in prostatic cancer patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 113-119 
    Details
    ISSN: 1432-1041
    Schlagwort(e): estramustine phosphate ; prostatic cancer ; pharmacokinetics ; metabolism ; estramustine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of estramustine phosphate (EMP) was studied in five prostatic cancer patients given single i.v. and oral doses of EMP in a cross-over study. Plasma and urinary concentrations of parent drug, estramustine, estromustine (the estrone analogue), estradiol and estrone were followed for 32 h. The elimination of intravenous EMP from plasma was biphasic. The mean volumes of distribution were small, being 43 and 108 ml/kg for the central and peripheral compartments, respectively. The plasma clearance was 64 ml/kg/h, and the half-lives of the two phases were 0.16 and 1.27 h. Metabolism was the major route of elimination of EMP. It was readily dephosphorylated and oxidized to yield the cytotoxic metabolites estramustine and estromustine. Estromustine was the main metabolite in plasma. When given orally EMP underwent extensive presystemic dephosphorylation, which started in the gastrointestinal tract. The relative bioavailability of estromustine after administration of EMP-capsules was 44%, which reflects incomplete absorption of EMP rather than first-pass metabolism of estromustine. The terminal half-life of estromustine was 10–20 h, which suggests that EMP might be given once or twice a day.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546718
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  • 162
    Digitale Medien
    Digitale Medien
    Correlation between the pharmacokinetics and pharmacodynamics of dopamine in healthy subjects (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 163-169 
    Details
    ISSN: 1432-1041
    Schlagwort(e): dopamine ; pharmacokinetics ; pharmacodynamics ; adrenaline plasma level ; noradrenaline plasma level ; blood pressure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and the pharmacodynamic action of dopamine were investigated in 5 healthy subjects. Dopamine was given in different doses (200, 400 and 800 µg/min) by constant intravenous infusion over 90 min. In order to control the influence of the procedure on the measured parameters the subjects also received a similar infusion of saline. Dopamine, noradrenaline and adrenaline levels in plasma were followed for up to 6 h after the infusion, and arterial pressure and heart rate were monitored. Dopamine reached a steady state level within 15 to 30 min after commencement of the infusion; the steady state levels averaged 36.5 µg/l at 200 µg/min, 73.8 µg/l at 400 µg/min and 207 µg/l at 800 µg/min. The corresponding total clearances were 5.8 l/ min, 5.51/min and 3.9 l/min suggesting non-linear kinetics. The kinetics could not be described by compartmental model. Noradrenaline and adrenaline levels were found to be elevated during infusion of dopamine. Noradrenaline had returned to its pretreatment level within 15 to 30 min after cessation of the infusion, whereas the adrenaline level did not return to the pretreatment value within the observation period. Heart rate was increased by the dose of 400 µg/min, and the systolic and mean arterial pressures were elevated, whereas distolic blood pressure remained unchanged. Elevated systolic blood pressure was better correlated with plasma dopamine than with noradrenaline concentration. This finding, in conjunction with the unchanged diastolic blood pressure, indicates that elevation of the systolic blood pressure is a direct rather than an indirect effect of dopamine. The increased heart rate was not correlated with the dopamine level.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630281
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  • 163
    Digitale Medien
    Digitale Medien
    Bioequivalence studies in humans of indomethacin capsules marketed in India (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 261-264 
    Details
    ISSN: 1432-1041
    Schlagwort(e): indomethacin capsules ; bioequivalence ; volunteers ; pharmacokinetics ; statistical significance ; bioavailability ; comparative bioequivalence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Two, separate 6×6 Latin square cross-over bioequivalence studies were performed in adult male volunteers using 10 different indomethacin capsule preparations marketed in India together with the pure drug powder as the standard. The products were evaluated with respect to plasma level at various times up to 8 h following administration of a 50 mg (2 × 25 mg) dose. Plasma samples were analysed by a fluorimetric method. Various pharmacokinetic parameters were calculated according to a two compartment model. Statistical evaluation of the data employed analysis of variance for a cross-over design (ANOVA) and Duncan's multiple range test to ascertain the significance of differences between the products. Of the 10 products studied, two were found to be bioinequivalent.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630296
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  • 164
    Digitale Medien
    Digitale Medien
    Lack of clinically important interaction between erythromycin and theophylline (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 485-489 
    Details
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; erythromycin ; interaction ; metabolism ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 11 healthy volunteers the kinetics of theophylline and the plasma levels and the urinary excretion of its metabolites were studied before and after treatment with erythromycin for 10 days. Theophylline was administered as an intravenous bolus injection (280 mg) followed by a constant intravenous infusion (23.8±4.1 mg/h) for 6 hours. The total clearance of theophylline at steady-state (63.4±9.9 vs 63.8±14.4 ml/min, before vs after erythromycin treatment) and the elimination half-life after cessation of the infusion (6.7±2.6 vs 7.5±1.8 h, before vs after treatment) did not change during the treatment with erythromycin. No difference in the formation of metabolites before and after treatment with erythromycin was detected; the findings in urine were 40.4±5.0 vs 42.1±5.4% 1,3-dimethyluric acid, 29.6±4.6 vs 30.1±5.9% 1-methyluric acid and 13.4±3.5 vs 12.5±2.2% 3-methylxanthine before and after erythromycin treatment, respectively. It is concluded that a clinically relevant interaction between erythromycin and theophylline does not occur.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542146
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  • 165
    Digitale Medien
    Digitale Medien
    Single and multiple dose kinetics of clobazam, and clinical effects during multiple dosage (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 499-503 
    Details
    ISSN: 1432-1041
    Schlagwort(e): benzodiazepines ; clobazam ; desmethylclobazam ; pharmacokinetics ; sedation ; accumulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Sixteen healthy volunteers, aged 19 to 62 years, took a single 20-mg oral dose of clobazam and the serum concentrations of clobazam and desmethylclobazam were measured for the following 7 days. The mean kinetic variables for clobazam were: volume of distribution 1.31/kg, elimination half-life 24 h, total clearance 0.47 ml/min/kg. 13 of the volunteers then took clobazam 5 mg twice daily for 22 consecutive days. Serum concentrations were measured during and after this period. Both clobazam and desmethylclobazam showed slow and extensive accumulation, their steady-state kinetics being entirely consistent with those observed after single doses. Elimination of both compounds after termination of treatment was equally slow. Clinical self-rating of morning sedation indicated a significant increase over baseline in subjective perception of sedation during the treatment period, and this effect persisted into the washout period. However, sedation did not increase in parallel with accumulating levels of clobazam and desmethylclobazam, probably due to functional adaptation or tolerance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542148
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  • 166
    Digitale Medien
    Digitale Medien
    Pharmacokinetic interaction of contraceptive steroids with prednisone and prednisolone (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 505-511 
    Details
    ISSN: 1432-1041
    Schlagwort(e): prednisolone ; prednisone ; oral contraceptives ; 6β-hydroxylase ; transcortin ; protein-binding ; steroid metabolism ; pharmacokinetics ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The oestrogenic component of oral contraceptives affects the activity of liver enzymes and the concentrations of plasma proteins implicated in steroid metabolism and transport. The present study was designed to determine these effects on the kinetics of prednisone and prednisolone. After an oral dose of prednisone, women on oral contraceptive steroids (n=10) had higher mean (±SD) area under the plasma concentration versus time curves of total (428±67 µg/ml/min vs 188±28 µg/ml/min, p〈0.001) and unbound prednisolone (64±10 µg/ml/min vs 41±10 µg/ml/min, p〈0.001) than women not taking oral contraceptive steroids (n=10). The differences were attributable to a lower non-renal clearance of prednisolone and to a higher apparent systemic availability of the drug in contraceptive users than in the controls. The affinity of albumin and transcortin for prednisolone was lower in women on oral contraceptives than in controls (p〈0.001). Thus, altered kinetics and protein binding may account for the known increase in glucocorticoid efficacy by oestrogens.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542149
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  • 167
    Digitale Medien
    Digitale Medien
    Acetaminophen accumulation in pediatric patients after repeated therapeutic doses (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 57-59 
    Details
    ISSN: 1432-1041
    Schlagwort(e): acetaminophen ; pediatric patients ; fever therapy ; accumulation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Acetaminophen serum concentrations were studied in 21 infants and children with fever. The maximum serum concentrations ranged from 9.96 to 19.6 µg/ml after a single dose of 12–14 mg/kg and 13.9 to 40.1 µg/ml after a single dose of 22–27 mg/kg. Ten patients were restudied at steadystate after repeat doses had been given every 4 or 8 h for 1 to 3 days. Total area under the acetaminophen serum concentration-time curve normalized for dose averaged 0.181 (ml/min/kg)−1 after the first dose and 0.202 (ml/min/kg)−1 at steady-state (p〈0.05). Five patients showed a 13 to 44% increase in the AUC; one had a 10% decrease in the AUC; and four had less than 6% change in the AUC. There was no evidence of hepatotoxicity. These data suggest that acetaminophen may accumulate after repeated therapeutic doses in children with fever.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00553155
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  • 168
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of metoprolol in healthy, elderly, non-smoking individuals after a single dose and two weeks of treatment (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 217-222 
    Details
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; pharmacokinetics ; age effect ; repeated doses ; pre-systemic elimination ; total body clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of long-term treatment on the absorption and dispsoition of metoprolol has been evaluated in 8 healthy, non-smoking, elderly individuals (mean age 74.5 years) and in a control group of 8 healthy, young individuals. Two trace doses of [3H]metoprolol were given i.v., first concomitantly with a single oral 50 mg dose of cold metoprolol, and second, with the morning dose after 2 weeks of treatment with 50 mg b.d. In the elderly, the mean AUC increased by about 45% (p〈0.05) over the treatment period, while in the control group the mean AUC was 18% greater (p〈0.05) on Day 14 than on Day 1. In the elderly, changes both in pre-systemic elimination and in total body clearance accounted for the elevation of the AUC, whereas reduced first-pass effect appeared to be the major cause of the increased steady-state plasma level in the control group. With the exception of the volume term, V β , the pharmacokinetic parameters were not significantly different between the elderly and the young individuals. For this reason, almost identical steady-state plasma levels were attained in the two groups. The results suggest that age-related physiological changes may have some minor effects on the pharmacokinetics of metoprolol, and also that the changes do not lead to significantly altered plasma concentrations compared to those in young individuals.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544048
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  • 169
    Digitale Medien
    Digitale Medien
    Lack of effect of haemodialysis on mebendazole kinetics: Studies in a patient with echinococcosis and renal failure (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 243-245 
    Details
    ISSN: 1432-1041
    Schlagwort(e): mebendazole ; haemodialysis ; echinococcosis ; pharmacokinetics ; protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of haemodialysis on mebendazole kinetics has been studied in a patient receiving both mebendazole therapy and haemodialysis. The procedure of haemodialysis did not influence the plasma concentration — time profiles or the mean daily plasma levels. The arterio-venous difference in the dialyser was negligible and no mebendazole could be detected in the dialysate. Protein binding of mebendazole was 90% before dialysis and 88% during dialysis and not significantly different from the binding in patients without renal disease (91.4±1.9%, n=22).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544053
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  • 170
    Digitale Medien
    Digitale Medien
    Naproxen disposition in patients with alcoholic cirrhosis (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 291-296 
    Details
    ISSN: 1432-1041
    Schlagwort(e): naproxen ; cirrhosis ; pharmacokinetics ; protein binding ; nonsteroidal antiinflammatory drugs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Chronic liver disease is known to alter the absorption and disposition of many drugs. To assess the influence of chronic alcoholic liver disease on the disposition of naproxen, we administered the drug both as a single dose and to steady state to 10 individuals with alcoholic cirrhosis and to 10 healthy controls. Plasma and serum samples collected after naproxen dosing were assayed for both total and (following equilibrium dialysis) unbound drug concentration. Clearance calculated based on both total and unbound naproxen concentration revealed no change in total plasma clearance of the drug at steady state but a marked reduction of approximately 60% in clearance based on unbound drug. Naproxen volume of distribution changed only minimally. Because clearance based on unbound drug concentration at a given dosing rate determines the plasma or blood free drug concentration, this concentration may increase significantly in patients with alcoholic liver disease given usual doses of naproxen. Unbound drug concentration is thought to determine the pharmacologic effect of a drug. We therefore recommend that naproxen dosing be reduced by at least half in patients with chronic alcoholic liver disease. In the absence of data to the contrary, this recommendation can be extended to individuals with other forms of hepatic disease.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542162
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  • 171
    Digitale Medien
    Digitale Medien
    The pharmacokinetics of a new radiosensitiser, Ro 03-8799 in humans (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 483-489 
    Details
    ISSN: 1432-1041
    Schlagwort(e): radiosensitiser ; pharmacokinetics ; healthy volunteers ; tumour patients ; Ro 03-8799
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A new hypoxic cell radiosensitiser, Ro 03-8799 has been administered intravenously to human volunteers and its kinetic parameters derived from plasma and urine data. Good penetration of drug into tumour tissue is found, consistent with its large volume of distribution. The plasma clearance of this compound is rapid due to high metabolic and renal clearances. These parameters combine to produce an elimination half-life of 5.6 h, approximately half that of misonidazole, a well studied radiosensitiser. It is hoped that this decrease in total body exposure will also reduce the cumulative toxicity seen when misonidazole is administered repeatedly.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00549599
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  • 172
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of valpromide after oral administration of a solution and a tablet to healthy volunteers (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 501-503 
    Details
    ISSN: 1432-1041
    Schlagwort(e): valpromide ; valproic acid ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of valpromide, a primary amide of valproic acid, was investigated in 6 healthy, adult male volunteers, each of whom was given 900 mg as a marketed, enteric-coated tablet and a solution. Valpromide was biotransformed to valproic acid after the administration of the tablet and the solution with a bioavailability of 0.79±0.24 and 0.77±0.12, respectively, relative to a marketed tablet of valproic acid. The absorption of valpromide was not rate-limited by dissolution. As a solid, non-hygroscopic, neutral prodrug of valproic acid, valpromide may be a good alternative to valproic acid and sodium valproate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00549603
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  • 173
    Digitale Medien
    Digitale Medien
    Inter- and intra-subject variation in the first-pass elimination of highly cleared drugs during chronic dosing (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 47-53 
    Details
    ISSN: 1432-1041
    Schlagwort(e): verapamil ; first-pass metabolism ; pharmacokinetics ; interindividual variation ; intraindividual variation ; chronic administration ; deuterated verapamil
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of verapamil in five healthy volunteers were investigated on 4 occasions during chronic administration of deuterated verapamil. There was no statistically significant difference in oral clearance, terminal half-life, bioavailability, morning trough level and peak concentration or in the time of their occurrence on the four occasions. The plasma clearance, however, exhibited considerable inter- and intra-individual variation, ranging between 26.3% and 85.4% and 12.0% and 48.0%, respectively. Comparison of these pharmacokinetic parameters with data from previous single dose studies in the same subjects revealed a significant (p〈0.05) decrease in the clearance and an increase in the apparent bioavailability of verapamil during chronic administration, although no difference in the half-life was found. Due to the considerable variation in the oral clearance of verapamil during chronic dosing, steady-state conditions in a strict pharmacokinetic sense may never be attained, and pharmacokinetic data obtained in single dose studies will be of limited value in predicting steady-state plasma concentrations.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546708
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  • 174
    Digitale Medien
    Digitale Medien
    Pharmacokinetic evaluation of haemoperfusion in phenobarbital poisoning (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 109-112 
    Details
    ISSN: 1432-1041
    Schlagwort(e): phenobarbital poisoning ; charcoal haemoperfusion ; distribution volume ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Charcoal haemoperfusion was performed for 5–12 h in three patients with maximal plasma phenobarbital concentrations of 600, 946 and 1044 µmol/l (138, 217 and 240 µg/ml). During haemoperfusion with constant blood flow phenobarbital elimination followed first order kinetics with half-lives of 11.1, 10.0 and 7.2 h, respectively. After termination of the haemoperfusion there was no rebound effect in plasma phenobarbital concentration and the elimination was first order with half-lives of 51, 82 and 48 h, respectively. Thus, the plasma phenobarbital half-life was reduced by 78–88% during haemoperfusion. In the same period 76–86% of the total body clearance of phenobarbital was due to the haemoperfusion column at a calculated volume of distribution of phenobarbital of 1.1–1.2 l/kg. This is clear evidence for recommending haemoperfusion in cases of serious poisoning with phenobarbital.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546717
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  • 175
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of nadolol in healthy subjects (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 125-127 
    Details
    ISSN: 1432-1041
    Schlagwort(e): nadolol ; pharmacokinetics ; plasma levels ; urinary excretion ; bioavailability ; circadian rhythm
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 7 healthy subjects (3 males and 4 females), the kinetics of nadolol was investigated after oral doses of 60 and 120 mg. The t1/2 was 14.0±1.8 h. The peak plasma level was doubled on doubling the dose (from 69±15 to 132±27 ng/ml, respectively) and the urinary excretion (13.5%) rose similarly. The half-life of elimination was longer at night than in the day, probably because of the slower nocturnal flow of urine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546720
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  • 176
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of furosemide in man after intravenous and oral administration. Application of moment analysis (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 197-207 
    Details
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; bioavailability ; pharmacokinetics ; oral administration ; i.v. administration ; drug absorption ; moment analysis ; food effect ; dissolution effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Furosemide 40 mg was administered to 8 healthy subjects as an i.v. bolus dose, as 1 tablet in the fasting state, and as 1 tablet and a solution after food intake. The i.v. data gave a total body clearance of 162±10.8 ml/min and a renal clearance of 117±11.3 ml/min; the volume of distribution at steady state was 8.3±0.61. Oral administration gave a bioavailability of the tablet (fasting) of 51%. Food intake slightly reduced the bioavailability, but not to a significant extent. There was no significant difference in availability between the tablet and the solution. Moment analysis gave a mean residence time after the i.v. dose, MRTi.v., of 51±1.5 min. The mean absorption times (MAT) for all oral doses were significantly longer than the MRTi.v., indicating absorption rate-limited kinetics of furosemide. On average, food delayed the absorption by 60 min. The MAT for the tablet in the postprandial state was significantly longer than for the solution, indicating dissolution rate-limited absorption of the tablet.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630286
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  • 177
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of epidural morphine in man (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 233-237 
    Details
    ISSN: 1432-1041
    Schlagwort(e): morphine ; anesthesiology ; epidural application ; pharmacokinetics ; plasma level ; CSF level
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Cerebrospinal fluid (CSF) and plasma morphine concentrations were determined in 5 patients after epidural administration of 6 mg morphine; plasma samples were collected frequently during the initial 6 h and 6–7 CSF samples were obtained from each patient over a 24 h period. Morphine was analysed using gas chromatography and electron capture detection. Individual morphine concentration-time curves were plotted for plasma and CSF and various pharmacokinetic variables were calculated. Plasma morphine concentrations after epidural injection were similar to those found after intramuscular administration; Cmax (66±8 mg/ml: mean±SEM) appeared within 12±3 min, and the terminal elimination half-life in plasma was 213±24 min. In CSF, morphine reached a peak (1575±359 ng/ml) after 135±40 min. The terminal elimination half-life for morphine in CSF was 239±10 min. The CSF bioavailability of morphine after epidural administration was calculated to be 1.9±0.5%. The study showed that epidural administration of morphine resulted in CSF concentrations many times higher than those in plasma, but still only 2% of the dose administered was available to the CSF compartment. Morphine was eliminated with similar speed from CSF and plasma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630291
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  • 178
    Digitale Medien
    Digitale Medien
    Pharmacokinetic and pharmacodynamic modelling with pancuronium (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 243-250 
    Details
    ISSN: 1432-1041
    Schlagwort(e): pancuronium ; neuromuscular relaxants ; simultaneous modelling ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and pharmacodynamics of pancuronium were studied following intravenous infusion in eleven patients undergoing surgical anaesthesia. Measurement of the plasma concentrations (Cp) of the neuromuscular blocking agent (NMBA) and the concomitant intensities of paralysis allowed their simultaneous modelling. The pharmacokinetic parameters derived for pancuronium were in the range of previously reported values, except that the mean total systemic plasma clearance (0.79±0.28 ml·min−1·kg−1) was reduced and the mean terminal phase half-life (169 min) was longer in these patients. Plasma concentration and % paralysis data were successfully fitted to a previously proposed pharmacodynamic model. This model assumes a separate effect compartment which exchanges drug directly with the central kinetic compartment (integrated effect model). The ‘steady-state’ Cp necessary to produce 50% paralysis (ECpss(50)) was estimated to be 0.21±0.08 µg·ml−1 (mechanical response) and 0.18±0.05 µg·ml−1 (EMG response). An analysis using the Hill equation of the Cp-response relationship, during and after the constantrate infusion of pancuronium bromide, resulted in effective plasma concentrations for 50% paralysis (ECp50) of 0.35±0.06 µg·ml−1 and 0.20±0.09 µg·ml−1, respectively, for mechanical twitch response. The corresponding values for EMG response were 0.32±0.06 µg·ml−1 and 0.17±0.06 µg·ml−1. Using this latter approach, the ECp50 estimated during onset of paralysis was significantly higher than that estimated during offset of paralysis (p〈0.05); no such difference was apparent between this latter parameter and the ECpss(50) of the integrated effect model (p〉0.05). No significant differences were observed between any of the pharmacodynamic parameter estimates generated from the data obtained from the two methods of assessment of neuromuscular function (mechanical vs. EMG response) (p〉0.05).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630293
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  • 179
    Digitale Medien
    Digitale Medien
    Effect of aluminium phosphate on the bioavailability of cimetidine and prednisolone (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 271-273 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; prednisolone ; aluminium phosphate ; antacids ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ten fasting subjects received 200 mg cimetidine orally either with water or 11 g aluminium phosphate mixture in a randomized, single dose, two-way cross-over study. Blood samples were taken for 12 h and urine was collected for 24 h. Cimetidine in plasma and urine was analysed by HPLC. There were no significant differences between the treatments with respect to peak plasma concentration, time to peak plasma concentration, area under the plasma concentration-time curve, and urinary excretion. In 12 healthy subjects the absorption of prednisolone was investigated when given alone and together with 11 g aluminium phosphate. Blood samples were taken over 16 h and prednisolone in plasma was analysed by HPLC. There were no significant differences in the values of area under curve (AUC), Cmax and tmax. The results indicate that aluminium phosphate does not reduce the bioavailability of cimetidine and prednisolone.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630299
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  • 180
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of cimetidine in advanced cirrhosis (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 347-355 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; cirrhosis ; pharmacokinetics ; bioavailability ; clearance reduction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of impaired liver function on the pharmacokinetics of cimetidine was studied in 8 patients with advanced cirrhosis given single doses of 100 mg i.v. and 400 mg p.o. on separate days. Compared to a control group of 10 healthy volunteers, the total renal and nonrenal clearance was significantly reduced in the cirrhotic patients; (total plasma clearance mean ± SD) 356±181 vs 789±262 ml/min (p〈0.01); renal clearance (Clr) 296±100 vs 588±181 ml/min (p〈0.01) and nonrenal clearance (Clnr) 97±111 vs 205±89 ml/min (p〈0.05). Compared to published results for age-matched ulcer patients, both total and nonrenal clearance were lower whereas renal clearance was within the reported normal range. A significant reduction in volume of distribution (Vdβ) was found, from 2.1±0.1 l/kg in controls to 1.0±0.4l/kg, and in the patient group there was a significant correlation between Vdβ and total plasma clearance (r=0.72, p〈0.05). Volume of distribution in steady state (Vdss) did not differ from published results in age-matched controls. No significant change in half-life was found. Bioavailability, estimated by AUC-measurement, showed considerable patient variability (21–143%), with a mean of 70±39%. This was lower than in the controls. In contrast, measurement of urinary excretion showed higher bioavailability in the patients (66±23 vs 51±8%). No correlation was found between any of the kinetic parameters and the clinical and laboratory data. It is suggested that patients with advanced cirrhosis should be closely observed when given cimetidine, and a reduction in dose should be concidered if side effects are to be avoided.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548766
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  • 181
    Digitale Medien
    Digitale Medien
    Steady state pharmacokinetics of trimethoprim 300 mg once daily in healthy volunteers assessed by two independent methods (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 393-397 
    Details
    ISSN: 1432-1041
    Schlagwort(e): trimethoprim ; concentration ; urinary excretion ; healthy volunteers ; steady state ; pharmacokinetics ; serum creatinine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The steady state pharmacokinetics of trimethoprim was determined after 300 mg orally once daily to 6 healty volunteers for 9 days. The microbiological assay of plasma level was unreliable at trimethoprim concentrations 〉4 µg/ml, so results from an HPLC-assay are given. Steady state was present after 3 days. The plasma concentration peaked 1 to 4 h (mean 2.0 h) after the dose at a mean of 6.0 µg/ml (range 3.1–9.5 µg/ml); the minimum value was 1.5 µg/ml (range 0.6–2.9 µg/ml). The mean AUCss was 77 µg/ml · h and the mean plasma clearancess was 67 and 74 ml/min on Days 8 and 9. Renal clearance was about 60% of the plasma clearance. The average plasma half life was 10.6 h (range 8.7–15.3 h). Thus, there was considerable interindividual variation in all pharmacokinetic parameters. 72 h after the last dose trimethoprim was detectable in plasma in only 1 of the 6 subjects. The minimum urinary concentration of trimethoprim during treatment was always well above (range 22 to 220 µg/ml) the MIC values for most urinary tract pathogens. Therefore, a daily dose of 300 mg trimethoprim results in a therapeutic concentration in urine at steady state that lasts throughout the dosing interval and in most subjects probably lasts also for a further 24 h. Trimethoprim administration raised mean serum creatinine from 67 to 97 µmol/l, probably due to competitive inhibition of the tubular secretion of creatinine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548773
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  • 182
    Digitale Medien
    Digitale Medien
    Comparison of the short-term effects of the loop diuretic piretanide and furosemide in patients with renal insufficiency (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 413-418 
    Details
    ISSN: 1432-1041
    Schlagwort(e): piretanide ; furosemide ; renal insufficiency ; loop diuretic ; natriuresis ; pharmacokinetics ; diuretic effect ; kaliuresis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The natriuretic effect of the new loop diuretic piretanide was investigated in patients with severe renal insufficiency and was compared with that of furosemide. In the first study 4 hospitalized patients (serum creatinine 407 to 1220 µmol/l) were examined after administration of piretanide (12, 24, 48 and 96 mg to two patients, and 24, 48, 96 and 192 mg to 2 other subjects, given every third day). In the second study 6 hospitalized patients (serum creatinine 194 to 698 µmol/l) were studied after receiving orally 2 different doses of piretanide and 2 different doses of furosemide orally, given every fourth day. The mean natriuretic effect of 48 mg and 96 mg piretanide was 250 and 340% of the control value for the entire group, and 311 to 480% in the subgroup of patients with serum creatinine below 530 µmol/l. For a given dose the natriuresis was inversely correlated with renal function, and at a given serum creatinine level the natriuretic response was dose-dependent. The drug had less effect on water and potassium diuresis than on natriuresis. No significant difference in natriuretic effect was found on comparison with furosemide given in the ratio furosemide: piretanide 3.33:1. The pharmacokinetic data showed a direct correlation between the dose and the mean plasma concentration and also between urinary recovery of the drug and the measured natriuretic response.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542133
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  • 183
    Digitale Medien
    Digitale Medien
    Individualizing theophylline dosage: Evaluation of a single-point maintenance dose prediction method (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 491-498 
    Details
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; computer simulation ; pharmacokinetics ; single-point dose prediction ; nomogram
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A dosage prediction method to estimate theophylline clearance and dose requirement was evaluated in 22 outpatients with partly reversible obstructive airways disease. The steady state theophylline dose required to achieve a target concentration (Css) was predicted using a single serum theophylline determination 8 h after a single oral test dose. In 17 nonsmoking patients a mean absolute deviation of 8.2% (range 0.0–21.7%) between predicted and observed Css was found, and in 5 smoking patients the mean deviation was 34.0% (range 2.2–53.8%). In 17 healthy smokers the single-point method was found to predict theophylline clearance at a sampling time of 8 h with a prediction error of 11.3 (range 0.8–25.3%) compared to the clearance determination using the area under the curve. In addition, a numerical simulation program to assess the influence of absorption, elimination and sampling time on predictive accuracy showed that the method could be successfully applied to a patient population with elimination rate constants between 0.07 1/h and 0.25 1/h, allowing a mean prediction error of 15%.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542147
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  • 184
    Digitale Medien
    Digitale Medien
    Comparison of radioreceptor assay and radioimmunoassay for atropine: Pharmacokinetic application (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 613-617 
    Details
    ISSN: 1432-1041
    Schlagwort(e): atropine ; radioreceptor assay ; radioimmunoassay ; serum levels ; pharmacokinetics ; assay comparison
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A membrane suspension prepared from rat brain was able to bind the potent muscarinic antagonist quinuclidinyl benzilate (QNB). The KD for binding was 0.48 nM and Bmax was 1.42 pmol/mg protein. Atropine competitively inhibited the binding of tritiated QNB to muscarinic receptors. This new radioreceptor assay (RRA) for atropine has been compared with a radioimmunoassay (RIA) for atropine. The RRA measures only the active component of atropine, 1-hyscyamine and in this respect it differs from the RIA. As little atropine as 1.25 ng/ml (4.33 nmol/l) in a 25 µl serum sample could be reliably assayed by the RRA. Using both assay techniques the pharmacokinetics of atropine was studied after a single 0.02 mg/kg i.v. dose given to 8 anaesthetized patients. The half-life calculated by the RRA was 3.7±2.3 h (m ± SD) and by the RIA 4.3±1.7 h. Both the volume of distribution and the total clearance were higher according to the RRA than the RIA: 3.9±1.5 vs 1.7±0.71/kg and 15.4±10.3 vs 5.9±3.6 ml/min/kg, respectively. The AUC measured by the RRA and RIA was 29.8±18.9 and 103.9±110.7 µg·h/l, respectively. The differences in the pharmacokinetics according to the 2 methods are presumably due to preferential tissue uptake of the l-form.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543495
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  • 185
    Digitale Medien
    Digitale Medien
    Oral pharmacokinetics of omeprazole (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 641-643 
    Details
    ISSN: 1432-1041
    Schlagwort(e): omeprazole ; gastric acid secretion ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of omeprazole were studied in a group of healthy male subjects after single and repeated oral doses of 30 and 60 mg. Absorption of omeprazole from its enteric-coated formulation was unpredictable. There was a highly significant increase in the area under the plasma concentration time curve (AUC) after repeated dosing. Omeprazole increases its own relative availability following repeated dosing. This may be due to inhibition of gastric acid secretion by omeprazole which is an acid-labile compound.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543502
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  • 186
    Digitale Medien
    Digitale Medien
    Bioavailability and pharmacokinetics of phenytoin during pregnancy (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 105-110 
    Details
    ISSN: 1432-1041
    Schlagwort(e): phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00553163
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  • 187
    Digitale Medien
    Digitale Medien
    Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 111-114 
    Details
    ISSN: 1432-1041
    Schlagwort(e): chlorambucil ; chronic lymphocytic leukaemia ; phenylacetic acid mustard ; food intake ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4–7.1) under fasting and 3.3 (range 1.3–7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02395216
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  • 188
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of S-adenosyl-L-methionine in healthy volunteers (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 119-121 
    Details
    ISSN: 1432-1041
    Schlagwort(e): S-adenosyl-L-methionine ; pharmacokinetics ; protein binding ; dose-dependent kinetics ; healthy volunteers ; urinary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary S-Adenosyl-L-methionine (AdoMet) kinetics was studied in 6 male subjects given 100 and 500 mg i. v. Drug concentrations in plasma and urine were assayed using a radioenzymatic method. Pharmacokinetic parameters were estimated according to an open two-compartment model. The apparent volumes of distribution after the 100 and 500 mg doses were 407±27 and 443±36 ml/kg (mean±SEM), terminal half-lives 81±8 and 101±7 min and body clearances 3.7±0.5 and 3.1±0.2 ml/min per kg. Urinary excretion was 34±3 and 40±2% of the administered dose. The results demonstrate that drug disposition occurs more via metabolism than via renal excretion, and it is not dependent on the administered dose. Binding of AdoMet to serum proteins is negligible.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02395218
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  • 189
    Digitale Medien
    Digitale Medien
    Papaverine disposition in cardiac surgery patients and the effect of cardiopulmonary bypass (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 127-130 
    Details
    ISSN: 1432-1041
    Schlagwort(e): papaverine ; cardiopulmonary bypass ; pharmacokinetics ; cardiac surgery patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Cardiac surgery involving cardiopulmonary bypass (CPB) causes substantial physiologic changes which may potentially alter the pharmacokinetic properties of drugs used during and after the procedure. Studies with fentanyl have implied a relationship between prolonged elimination half-lives following CPB and decreased liver perfusion during and after the procedure. To further test this hypothesis, the effects of CPB on the pharmacokinetics of papaverine, a coronary vasodilator currently being added to the cardioplegic solution to prevent vasospasm, were studied. The drug was given to two groups of patients, one (n=6) undergoing surgery with and one (n=5) without CPB, the latter serving as controls. Plasma papaverine concentrations declined biexponentially in the control patients with a mean elimination half-life of 1.30±0.25 h, total plasma clearance of 13.8±3.75 ml/min/kg, volume of distribution of 1.52±0.45 l/kg and volume of distribution, steady-state, of 0.992±0.530 l/kg. For the CPB group, only half-life was estimated, and averaged 2.77±0.28 h, significantly greater (p〈0.01) than that in the controls. These results further confirm the increased half-lives seen with other hepatically cleared drugs following CPB and have implications in the clinical management of patients given drugs eliminated in this manner.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544033
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  • 190
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of meptazinol after single and multiple oral administration to elderly patients (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 223-226 
    Details
    ISSN: 1432-1041
    Schlagwort(e): meptazinol ; pharmacokinetics ; multiple dosing ; elderly patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Oral administration of meptazinol (200 mg Meptid®) to male and female geriatric patients (〉70 years) resulted in rapid absorption, with peak drug concentrations at 0.5 to 3 h after dosage. Subsequent elimination also proceeded rapidly with a half-life of 3.39 h (±0.26 SEM) after a single dose and 4.97 h (±0.80 SEM) after 13 consecutive 6-h doses. These values were not statistically different. There was no accumulation of meptazinol above that expected from the single-dose kinetics. Plasma protein binding of meptazinol was 33.8% (±0.74 SEM). No sex difference was apparent in any of the pharmacokinetic parameters determined. Comparison of these results with those obtained in an earlier study in young volunteers showed that although the half-life of meptazinol was somewhat longer than the value of 2 h seen in the young, peak plasma concentrations after single and multiple dosing were similar for both age groups, implying that clearance remained largely unaltered. It was concluded that there was no pharmacokinetic basis for recommending a reduction in dosage when treating elderly patients with oral meptazinol.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544049
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  • 191
    Digitale Medien
    Digitale Medien
    Identification of a prazosin metabolite and some preliminary data on its kinetics in hypertensive patients (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 275-280 
    Details
    ISSN: 1432-1041
    Schlagwort(e): prazosin ; hypertensive patients ; prazosin metabolite ; HPLC assay ; pharmacokinetics ; hypotensive effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A metabolite of prazosin was detected in serum from hypertensive patients treated with prazosin. Its structure as 2-(1-piperazinyl)-4-amino-6,7-dimethoxyquinazoline was established by UV, IR, and mass-spectrometry. An assay method for simultaneous determination of prazosin and its metabolite in serum, urine and saliva is described. Preliminary data about the kinetics of prazosin and the metabolite after a single oral dose of prazosin 1 mg, and after multiple doses of 1 to 5 mg t.i.d. for 6–82 days in 7 patients with hypertension, are presented. After the single dose the metabolite level was much lower than that of intact drug, even though the former was eliminated much more slowly than the latter. The slow elimination of the metabolite led to its eventual accumulation in serum during multiple administration. The mean accumulation ratio of the metabolite was estimated to be at least 5.5 (from 3.0 to 7.9). Prazosin itself had a low accumulation ratio, so the mean steady-state level of the intact drug on multiple administration was several times lower than that of metabolite. As this metabolite has some hypotensive effect in animals, it may account for part of the therapeutic activity of parzosin in patients. The mean steady-state concentration of intact prazosin during the course of treatment were found to be significantly lower than that predicted from a single dose study.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542159
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  • 192
    Digitale Medien
    Digitale Medien
    Effect of cimetidine and ranitidine on carbamazepine and sodium valproate pharmacokinetics (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 341-343 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; ranitidine ; carbamazepine ; sodium valproate ; pharmacokinetics ; drug metabolism ; inhibition
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of a single oral dose (400 mg) of carbamazepine and sodium valproate were compared in peptic ulcer patients before and after four weeks of a therapeutic course of either cimetidine (1 g/day, n=6 subjects) or ranitidine (300 mg/day, n=6 subjects). There was a small (up to 20%) but statistically significant decrease in oral clearance of carbamazepine after cimetidine treatment. A similar fall in sodium valproate clearance in five cimetidine-treated patients was accompanied by a significantly prolonged elimination half-life. No such trends were demonstrated during ranitidine treatment. Since both anticonvulsants are partly metabolized by hepatic mixed function oxidases, an inhibition by cimetidine at this level may be responsible for the observed impairment of clearance. Thus a potentially important clinical interaction may occur in patients taking anticonvulsants and cimetidine concurrently.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542172
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  • 193
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and pharmacodynamics of a novel orally active angiotensin converting enzyme inhibitor (HOE 498) in healthy subjects (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 577-581 
    Details
    ISSN: 1432-1041
    Schlagwort(e): HOE 498 ; ACE inhibitor ; pharmacokinetics ; pharmacodynamics ; urinary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme inhibitor HOE 498 were investigated in 10 healthy normotensive male subjects. Serum levels of the active metabolite M 1 (dicarboxylic acid) of HOE 498 were measured by HPLC up to 14 days after a single oral dose of 10 m g HOE 498. Peak serum concentration of M 1 between 5–50 ng/ml was observed 1.5–3.0 h after administration. The serum concentration-time curve of M 1 was polyphasic and exhibited a prolonged terminal phase with a half-life of approximately 110 h. Despite the long terminal half-life M 1 could not be detected in urine later than 72 h after administration. The activity of the angiotensin converting enzyme in plasma was completely suppressed for up to 12 h, and 72 h after dosing 50% inhibition of the enzyme was still observed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00556895
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  • 194
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and pharmacodynamics of transdermally administered clonidine (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 79-85 
    Details
    ISSN: 1432-1041
    Schlagwort(e): clonidine ; transdermal application ; pharmacodynamic effect ; pharmacokinetics ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Clonidine was applied to the skin of healthy volunteers once weekly by means of a Transdermal Therapeutic System (TTS). The plasma concentration and renal excretion of clonidine, and its effects on mean arterial blood pressure (MAP) and heart rate (HR) were recorded for 7 days, followed by a three-day observation period when a second TTS was applied. Subjective side effects were semiquantitatively recorded. Four differents TTS formulations were tested; of which TTS-RP 600679 was the most effective. Following application of this formulation, the plasma level of the drug built-up up during the first 2 days and then remained stable for 120 h at therapeutic concentrations between 0.5 and 0.7 ng/ml; MAP was consistently reduced. During the steady state period the daily urinary clonidine excretion was in the same range as during chronic administration of Catapres tablets 0.15 mg every 12 h, or Catapres Perlongets 0.25 mg every 24 h. Transdermal clonidine applications renewed weekly provide the following therapeutic advantages: 1. patients are protected continuously throughout the entire steady state period; 2. daily fluctuations in plasma clonidine concentration are minimized, which may result in a marked reduction in side effects; and, 3. drug compliance should be improved.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546713
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  • 195
    Digitale Medien
    Digitale Medien
    Effect of a reversible and selective MAO-A inhibitor (cimoxatone) on diurnal variation in plasma prolactin level in man (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 71-77 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cimotaxone ; MAO inhibitor ; plasma prolactin ; circadian rhythm ; healthy volunteers ; hypothalamic MAO ; prolactin secretion ; metabolism ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Prolactin (PRL) secretion is stimulated by serotonin (5-HT) and inhibited by dopamine (DA). 5-HT is generally recognized as a substrate for type A monoamine oxidase (MAO), whereas DA is considered as a substrate for either A or B, or both forms of MAO, depending on the species and tissues used. The effect of cimoxatone, a reversible, selective MAO-A inhibitor, on diurnal variation in plasma PRL level was investigated in healthy adults after a single 40 mg oral dose, as an indirect approach to investigating whether DA is preferentially a substrate for Type A or B MAO in man. The circadian rhythm in PRL, stress conditions and diet were taken into account in the present study, which was placebo-controlled. There was a slight but significant reduction in circulating PRL in the six subjects, which persisted for at least 9 h after cimoxatone. However, the duration of the decrease in plasma PRL was shorter than the inhibition of MAO-A. The results are not inconsistent with the presence of both forms of MAO in the human hypothalamus and with DA as a substrate for both forms in this region, if it is assumed that the hypothalamic concentrations of the drug during the period 0–9 hours was sufficiently high to inhibit DA deamination by both forms of MAO.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546712
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  • 196
    Digitale Medien
    Digitale Medien
    Dose-dependent pharmacokinetics of aprindine in healthy volunteers (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 129-131 
    Details
    ISSN: 1432-1041
    Schlagwort(e): aprindine ; antiarrhythmic agent ; healthy volunteers ; plasma level ; oral administration ; pharmacokinetics ; urinary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of aprindine following a single oral dose can best be described by a two-compartment open model. The mean plasma half-life (t1/2β) increased from 8.0±2.1 h (SD) after a 25 mg dose to 9.4±2.9 h after 50 mg and to 15.8±2.6 h after 100 mg, with a decrease in total plasma clearance (Cl/F) and volume of distribution at steady state (Vdss/F) and during β-phase (Vdβ/F). The area under plasma concentration-time curve (AUC), maximum plasma concentration (Cmax) and the amount of unchanged aprindine excreted in the urine increased in a non-linear fashion with the increase in dose. The t1/2β after multiple oral doses showed a 3-fold increase over the single dose value. These results indicate that aprindine shows dose-dependent non-linear kinetics.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546721
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  • 197
    Digitale Medien
    Digitale Medien
    Pharmacokinetic and pharmacodynamic study of the combination of furosemide retard and triamterene (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 191-195 
    Details
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; triamterene ; drug combination ; pharmacodynamics ; pharmacokinetics ; furosemide retard ; triamterene metabolite ; urine potassium
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacodynamics and pharmacokinetics of the combination of furosemide retard (30 mg)/triamterene (50 mg) were compared with furosemide (30 mg) in 18 healthy male volunteers aged 39.3±6.3 years. After the administration of furosemide the onset of its effect was very rapid, reaching a maximum between 1.5 to 3 h, and followed by rebound after 9 to 10.5 h. In contrast the combination furosemide retard/triamterene showed a protracted course with a duration of effect up to 12 h. The general effect over 12 h of the two preparations was equivalent with respect to the excretion of urine, sodium, chloride and calcium, but the combination caused significantly less excretion of potassium (p≤0.05) than furosemide. After a lag-phase of 33.9±5.4 min the maximum plasma concentration of furosemide was reached after 3.47±0.66 h, and the elimination half-life was approximately 2 h. After a lag-phase of 33.0±17.8 min the maximum plasma concentration of the main metabolite of triamterene, the OH-TA sulphuric acid ester, was reached after 1.7±0.59 h, and its elimination half-life amounted to 1.25±0.37 h. Because of the sustained release of furosemide from the retard-formulation, its principal pharmacokinetic parameters were better adapted to those of triamterene. The consequences were not only a protracted effect but also an improved electrolyte profile, especially with regard to reduced loss of potassium. In the case of renal insufficiency, however, the potassium level in serum might be increased to an undesirable extent.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630285
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  • 198
    Digitale Medien
    Digitale Medien
    Bioavailability of cyclophosphamide from oral formulations (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 269-270 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cyclophosphamide ; cytostatic drug ; cancer therapy ; female breast cancer ; bioavailability ; rapid release formulations ; gastric juice resistant formulation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Cyclophosphamide (CP) is an alkylating cytostatic compound, which is activated to its cytotoxic form in the liver [1]. Since the therapeutic range of CP in the treatment of human tumours, is small like other cytostatics, a constant high bioavailability is essential for its oral administration. Although CP has become one of the most widely used cytostatics [2], there do not appear to have been any bioavailability investigations providing the necessary information. The development of a very sensitive gas chromatographic analytical method has now permited investigation of the pharmacokinetics of oral CP in conventional clinical doses [3, 4, 5, 6].
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630298
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  • 199
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and hypotensive effect in healthy volunteers of pinacidil, a new potent vasodilator (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 603-608 
    Details
    ISSN: 1432-1041
    Schlagwort(e): pinacidil ; hypertension ; pinacidil pyridine-N-oxide ; urinary excretion ; protein binding ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Preliminary investigation in 3 healthy volunteers suggested that intravenous pinacidil in a dose of 0.2 mg/kg had a potent but well-tolerated hypotensive action in the supine position. Facial flushing, uncomfortable chest sensation and distressing postural hypotension occurred at serum concentrations above 300 ng/ml. Pinacidil, 0.2 mg/kg, was given intravenously over 4 min to 15 healthy volunteers in the supine position. Maximum fall in mean arterial pressure (MAP) was 15.7±6.0 mmHg. Maximum rise in heart rate was 23.8±6.6 beats/min. Pinacidil serum distribution half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\alpha }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\alpha }$}}}$$ ) was 13.4±8.5 min and elimination half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\beta }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\beta }$}}}$$ ) was 2.13±0.49 h. The apparent volume of distribution (Vdβ) was 90.3±13.21 and total body clearance was 31.1±9.61/h. Pinacidil was approximately 40% bound to plasma protein over the concentration range 40–400 ng/ml. Urinary excretion of unchanged pinacidil accounted for 5.7 ± 1.3% of the administered dose over 24 hours and urinary excretion of the major metabolite, pinacidil pyridine-N-oxide, was 31.6±9.2% of the administered dose. It was concluded that intravenous pinacidil is a potent vasodilator hypotensive compound, with a duration of action between 1.5 and 2 h.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543493
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  • 200
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and bioavailability of digitoxin by a specific assay (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 85-89 
    Details
    ISSN: 1432-1041
    Schlagwort(e): digitoxin ; radioimmunoassay ; pharmacokinetics ; bioavailability ; digitoxin metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and bioavailability of digitoxin were examined in six normal human subjects using an assay that separates digitoxin from its metabolites. After intravenous administration, the mean systemic clearance was 2.44 ml/min; the volume of distribution was 0.47 l/kg; and the elimination half-life was 6.5 days. After oral administration, the elimination half-life was 5.8 days. The bioavailability was 81.5% using the specific assay. Using a non-specific, direct serum digitoxin radioimmunoassay the bioavailability was 98.0%. Assay of aqueous fractions from extracted serum samples indicated higher levels of water-soluble metabolites following oral compared to intravenous digitoxin administration. These findings suggest that previously reported values for digitoxin bioavailability using non-specific methods may be falsely elevated due to the presence of digitoxin metabolites in serum.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02395212
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