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  • 1980-1984  (479)
  • 1980  (479)
  • Computational Chemistry and Molecular Modeling  (333)
  • Rat  (88)
  • pharmacokinetics
  • Nuclear reactions
Materialart
Erscheinungszeitraum
  • 1980-1984  (479)
Jahr
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 67 (1980), S. 143-146 
    ISSN: 1432-2072
    Schlagwort(e): Ethanol ; Tolerance ; 5,7-Dihydroxytryptamine ; 5-HT ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract 5,7-Dihydroxytryptamine (5,7-DHT) or the vehicle was administered once into both lateral ventricles of the rat. Desmethylimipramine (DMI) was administered IP prior to the intraventricular injection of 5,7-DHT to prevent the destruction of norepinephrine (NE) terminals. Following recovery from surgery, ethanol (5 g/kg, PO) or isocaloric sucrose was given daily for 25 days. Tests at 5-day intervals showed that chronic ethanol treatment produced tolerance to the motor impairment on the moving belt test and to hypothermic effects of ethanol. The 5,7-DHT treatment did not alter either the motor impairment or hypothermia produced by the initial dose of ethanol. However, 5,7-DHT treatment produced a 75% depletion of brain serotonin (5-HT) without altering NE concentration and retarded the development of tolerance to ethanol in both measurements. This study with a specific central depletor of 5-HT, without alteration in NE concentration, extends and supports our hypothesis that brain 5-HT modulates the development of tolerance to ethanol.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 68 (1980), S. 197-200 
    ISSN: 1432-2072
    Schlagwort(e): Continuous amphetamine ; Hallucinogens ; Limb flicks ; Shakes ; Grooming ; Model psychosis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats injected with LSD or mescaline show the behavioral syndrome which has been previously reported following injections of hallucinogens in higher mammals: limb flicks and whole body shakes. Although these behaviors are not elicited by acute injections of amphetamine, they are present in rats which have been pretreated for 108 h with a slow-release amphetamine pellet, given a 12h rest period, and then injected with d-amphetamine. Such pellet-pretreated animals also groom their body surface excessively. We propose that this novel syndrome which follows continuous amphetamine administration can serve as an animal model of the type of amphetamine psychosis that is produced by a similar drug regimen in humans.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 68 (1980), S. 257-259 
    ISSN: 1432-2072
    Schlagwort(e): Metrazol ; Conditioned taste aversion ; Rat ; Two bottle test preference ; Saccharin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Employing a two bottle drinking procedure where an animal's preference is measured between plain water and a novel fluid, it was found that the convulsant drug Metrazol produced a conditioned taste aversion to saccharin. This finding is contrary to that of previous reports and highlights the sensitivity of the two bottle method in detecting a taste aversion.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 69 (1980), S. 101-105 
    ISSN: 1432-2072
    Schlagwort(e): Diazepam ; Naloxone ; Behavioral inhibition ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of naloxone on diazepam-induced release of behavior in aversive situations were investigated in rats. Naloxone (0.5 and 1 mg/kg-1) suppressed diazepam-induced eating in an unfamiliar situation and reduced (1 mg/kg-1) spontaneous food intake. Naloxone (1 mg/kg-1) canceled the increased lever pressing produced by diazepam in a conflict procedure in which one electric shock was delivered at each seventh press. Naloxone (1 mg/kg-1) failed to reverse the enhanced responding for food induced by diazepam in the presence of a signal previously paired with electric foot shocks. In this situation, naloxone alone reinforced the behavioral suppression. These results suggest that transmission mediated by opiate peptides may be involved in only some ‘disinhibitory’ effects of benzodiazepines. In addition, such a peptidergic transmission may play a role in the control of stress-induced behavioral suppression.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 69 (1980), S. 183-185 
    ISSN: 1432-2072
    Schlagwort(e): DPH ; Genral activity ; Stereotypy ; Supersensitivity ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Animals were administered increasing doses of diphenylhydantoin (DPH) for 20 days. During withdrawal they were observed in an open field. The results suggest that chronic DPH administration leads to a central supersensitivity phenomenon. Possible interference of DPH with dopaminergic systems was discussed.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-2072
    Schlagwort(e): Rating scales ; Photocell activity cages ; Measurement ; Stereotypy ; d-Amphetamine ; Apomorphine ; Dopamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A novel means of measuring and analysing behavioural effects of dopamine agonists is described and illustrated by a comparison of the effects of d-amphetamine and apomorphine in the rat. d-Amphetamine (0–15 mg/kg IP) produced significant dose- and time-dependent changes in responses such as locomotion, rearing and sniffing, but not in licking or gnawing. In contrast, apomorphine (0–5 mg/kg SC) produced significant increases in licking and gnawing, as well as in locomotion and sniffing, but no changes in rearing. The results are discussed in comparison with those obtained by other methods, such as photocell beam interruptions or stereotypy rating scales, and may be of importance in elucidating the functions of the forebrain dopamine projections.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 386 (1980), S. 221-230 
    ISSN: 1432-2013
    Schlagwort(e): Optokinetic system ; Pretectum ; Visual vestibular convergence ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract 1) The responses of single units in the pretectum (Pt) and in the n. reticularis tegmenti pontis (NRTP) to constant velocity horizontal rotation (0.25–60 deg/s) of a large-field visual pattern were studied in immobilized, non-anesthetized DA-HAN rats. In addition, responses of Pt and NRTP neurons to pure vestibular stimuli (rotation in the dark) were studied. 2) Pt neurons showed seven response types to optokinetic stimulation (Table 1). The most frequent response (48%) consisted of a very rapid increase in firing to steady state on temporonasal motion stimulation of the contralateral eye; nasotemporal stimuli yielded no change in resting rate as did stimulation of the ipsilateral eye. The response maximum occurred at a retinal slip velocity of 1 deg/s. None of the Pt units tested responded to pure vestibular stimuli. 3) NRTP neurons — as Pt units — most frequently (43%) increased their discharge rate on temporonasal stimulation of the contralateral eye and maintained a constant resting rate during nasotemporal motion. Peak response amplitudes also occurred with retinal slip velocities of 1 deg/s. Contrary to the fast time-to-peak of the responses of Pt neurons NRTP units showed a slow rise in frequency of firing to peak response levels. 4) NRTP neurons responded to pure vestibular stimuli (horizontal angular acceleration in the dark). The vestibular responses were synergistic with those evoked in the same neurons by optokinetic stimuli. Thus, the most frequently encountered type of optokinetic response (s. above) showed a type II vestibular response. 5) Comparison of OKN and Vn optokinetic responses with those of Pt and NRTP suggests that the unidirectional-selective Pt and NRTP neurons are important links in the central optokinetic path. In addition, the NRTP may represent the site at which the retinal slip signal and the eye velocity signal converge. This convergence has been postulated in models of the system [12].
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-2013
    Schlagwort(e): Rat ; Micropuncture ; Tubuloglomerular feedback ; DOCA-salt treatment ; Extracellular volume
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Experiments were performed in anesthetized rats to investigate the time course of the adaptive changes in tubuloglomerular feedback reactivity and juxtaglomerular renin activity induced by DOCA and NaCl loading (isotonic saline as drinking fluid plus daily injections of 25 mg/kg DOCA). In these DOCA escaped rats we studied further the effect of acute volume depletion and repletion on the magnitude of feedback responses. A significant reduction of feedback reactivity was found on the fifth day after starting the DOCA-salt treatment with maximum depression being established after two weeks. In contrast, significant reduction of juxtaglomerular renin content required 10 days and maximum depression three weeks of DOCA-salt administration. In DOCA-salt treated animals with severely curtailed feedback responses acute volume depletion was induced by a single injection of furosemide (10 mg/kg) leading to an excretion of 0.49 ±0.17 mEq sodium and a mean decrease of body weight of 2.17±0.22% over a period of 60–70 min. Mean feedback response (expressed as percent change of early proximal flow rate caused by elevating loop of Henle flow rate from zero to 40 nl/min) was −43.9 ±4.0%, significantly greater than in the pre-depletion phase and indistinguishable from responses seen in normal control rats. Repletion of extracellular volume by infusing HCO3-Ringer solution over 20 min induced a reduction in feedback responsivity to −12.0±2.9%. Plasma and juxtaglomerular renin concentration increased with volume depletion and decreased with volume repletion, but remained considerably lower than observed in normal control rats. Our results suggest that the tubuloglomerular feedback system responds to acute alterations in extracellular volume with rapid adaptations in its reactivity which is consistent with its role in the control of sodium excretion.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 387 (1980), S. 67-68 
    ISSN: 1432-2013
    Schlagwort(e): Hepatic vein ; Catheterization ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A procedure for catheterization of a right hepatic vein is described in the rat. The procedure is based on the observation that, when the posterior half of the body is bent to the left, a right hepatic vein is aligned with the axis of anterior vena cava and posterior vena cava. A catheter, inserted in the right jugular vein and fitted with a rectilinear mandrel, is guided into the right auricle, the suprahepatic segment of posterior vena cava and a right hepatic vein. Successful catheterization of a right hepatic vein has been obtained in 47 out of 50 animals in which the procedure has been performed.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1432-2013
    Schlagwort(e): Secretin ; Vasoactive intestinal peptide ; Glucagon ; Isoproterenol ; Adenylate cyclase ; Heart ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Membrane adenylate cyclase from rat heart was activated by the two gut peptides secretin and vasoactive intestinal peptide (VIP), glucagon, and the β-adrenergic drug isoproterenol, in the presence of guanosine 5′-triphosphate (GTP). With all the stimuli tested, the optimal magnesium concentration was 5 mM, i.e. in excess over the 0.5 mM ATP substrate concentration and 0.01 mM GTP used as cofactor. Under these conditions, half-maximal adenylate cyclase activation with glucagon, secretin, and VIP was achieved at concentrations of 0.5, 0.5 and 1.0 μM, respectively. Data obtained with the secretin (7–27) fragment, a secretin antagonist, indicate that secretin and VIP acted on the same binding sites, which differed from glucagon binding sites. Structural requirements for secretin activation of cardiac adenylate cyclase were evaluated by comparing the potency and efficacy of parent peptides and synthetic analogs. The gastric inhibitory peptide GIP was inactive. When using 13 mono-or bi-substituted analogs, it appeared that amino acids in positions 1, 2, 3, 4 and 6 were of major importance while those in position 5 and 11 played a relatively minor role.
    Materialart: Digitale Medien
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 385 (1980), S. 161-165 
    ISSN: 1432-2013
    Schlagwort(e): Glomerular filtration rate ; Unilateral nephrectomy ; Compensatory hypertrophy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Changes in the glomerular filtration rate (GFR) were studied in rats, 4 h to 4 weeks after unilateral nephrectomy (NX). The GFR was determined with a technique using51Cr-EDTA and a single timed blood sample. The GFR determined in this way corresponded with the GFR calculated by two compartment analysis and with the plasma levels of creatinine and urea. Increases in the GFR, compared with half the GFR of sham operated rats, were observed as early as 4 h after NX. This increase was entirely due to an increase in the GFR per gram of kidney, since no increase in kidney weight was observed at that time. After the initial increase, the GFR remained at that level during the first 48 h after NX. At 48 h a significant increase in kidney weight per 100 g body weight had taken place. The longterm changes in the GFR amounted to an increase of about 80% of that of sham operated rats after 3–4 weeks. After 4 weeks, the increase in the GFR of the remaining kidney was due to an increase in kidney weight of 35% as well as an increase in the GFR per gram of kidney of 20%. These data indicate that the increase in the GFR of the remaining kidney after unilateral NX occurs rapidly and is independent of an increase in kidney weight. Compensatory hypertrophy develops at a later stage and helps to maintain the increased function of the single remaining kidney.
    Materialart: Digitale Medien
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 385 (1980), S. 211-215 
    ISSN: 1432-2013
    Schlagwort(e): Rat ; Renal hypertension ; Plasma renin activity ; Water intake ; Declipping ; Reclipping ; Converting enzyme inhibitor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Application of a renal artery clip in rats with an undisturbed contralateral kidney caused a sustained increase in blood pressure and a transient rise of plasma renin activity and water intake. The response of blood pressure, plasma renin activity and water intake was augmented after reapplication of the clip to normotensive declipped rats (renal hypertensive rats, from which the clip had been removed 24 h before the reapplication). The time-course of the changes of blood pressure, plasma renin activity and water intake were similar after the initial application as after reapplication of the clip. Administration of an inhibitor (SQ 14.225) of the converting enzyme abolished the increase in blood pressure and water intake after reapplication of the clip. These data indicate a critical role of renin in the rise of blood pressure and water intake after initial application of a renal artery clip as well as after reapplication of the clip to declipped rats.
    Materialart: Digitale Medien
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 387 (1980), S. 121-126 
    ISSN: 1432-2013
    Schlagwort(e): Local tissuepO2 ; Hypoglycemia ; Brain cortex ; ECoG ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Oxygen supply of the brain cortex together with changes in the electrocorticogram (ECoG) were investigated during and after insulin induced hypoglycemia in 13 anaesthetized rats. Local oxygen partial pressures (pO2) on the parietal cortex were continuously measured with a multiwire surface electrode of the Clark type. During early hypoglycemia with a mean arterial glucose concentration [G]a of 2.81 (SD ±0.40) mmol/l, the local tissuepO2 did not change significantly as compared to thepO2 values recorded during the control period with a normal [G]a of 4.51 (SD±0.70) mmol/l. During severe hypoglycemia at a [G]a of 1.39 (SD±0.2) mmol/l,pO2 began to increase continuously on all 104 measuring sites, independently of changes in arterial blood pressure and ECoG. During a period of 7–18 min of isoelectricity, tissuepO2 remained elevated so long as blood pressure did not decrease. After injection of a 25% glucose solution,pO2 gradually decreased to control values within 30–60 min in most experiments. We conclude from these results that oxygen supply is generally improved during severe hypoglycemia. We assume that the increase in tissuepO2 is mainly caused by an increase in microflow. Thus, the neuronal damage occurring after severe hypoglycemia, as reported in literature, cannot primarily be caused by an oxygen deficiency.
    Materialart: Digitale Medien
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  • 14
    ISSN: 1432-2048
    Schlagwort(e): Boron ; Foliar nutrition ; Nuclear reactions ; Transport (boron) ; Trifolium
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The growth of white clover (Trifolium repens L.) is severely inhibited by boron starvation, but a foliar treatment with boric acid can transitorily alleviate the deficiency symptoms. The 10B(n ,α)7 Li nuclear reaction has been used to study boron transport in the plant after foliar application. More than 98% of the boron supplied remained at the point where it was applied to the leaves, and less than 2% was useful to the growth of the treated plant. This small “efficient” portion of boron was quite mobile. It was distributed to the different parts of the plant, then was transferred from the oldest parts to the newly formed leaves. Physiological and agronomical implications of these data are discussed.
    Materialart: Digitale Medien
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  • 15
    ISSN: 1432-2307
    Schlagwort(e): Tumor promotion ; Tumor initiation ; DMBA ; TPA ; Two-stage carcinogenesis experiment ; Carcinogenesis ; Cocarcinogenesis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In contrast to a previous report by Shubik, the validity of the 2-stage skin carcinogenesis experiment was demonstrated in the rat. The modified experiment was carried out in female Sprague-Dawley rats using intragastrically administered DMBA as a carcinogen and the topically applied phorbol ester TPA as a promoter. Seven groups of animals were used. Two groups were treated with TPA only, two groups were initiated only with DMBA, two further groups were both initiated and promoted, and one group served as a control. Each of the initiated/promoted groups or only initiated or promoted groups contained one sub-group in which the animals had been bilaterally ovarectomized prior to the experiment. Hyperplasia of the dorsal epidermis occurred only in the promoted and in the initiated/promoted groups. Tumors of the back skin were observed exclusively after initiation/promotion. Ovarectomy — leading to a prolonged survival time of the animals — seems to be crucial for the manifestation of malignant skin tumors. Initiation/promotion also gives rise to tumors of the forestomach, the small intestine, the liver and the colon. Tumors in other organs (especially in the mammary gland and the Zymbal gland) were also be observed after initiation alone.
    Materialart: Digitale Medien
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    Virchows Archiv 386 (1980), S. 331-341 
    ISSN: 1432-2307
    Schlagwort(e): Fluorocarbon ; Extracorporeal circulation (EEC) ; Pulmonary ; systemic embolism ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary After intravenous injection of 0.1 ml Fluorocarbon (FC) into the caudal vein of rats clear droplets which are reminiscent of gas emboli appear in the pulmonary and cerebral arteries. These droplets cannot be stained with Azan, haematoxylin-eosin, Nile blue sulfate, Sudan black B, and Sudan III in Paraplast embedded or frozen sections. Gas chromatography of affected lung tissue reveals a high concentration of FC. The clear droplets are the histological correlates of FC emboli which lead to haemorrhagic lung infarction and ischaemic brain infarcts. After intralienal injection FC induces haemorrhagic infarcts of the spleen near the injection site and massive embolization of the intrahepatic portal veins with consequent liver cell necrosis. FC droplets are phagocytosed by hepatic sinusoidal lining cells. Due to the absence of a specific method for identifying FC embolization of renal vessies is difficult to assess.
    Materialart: Digitale Medien
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  • 17
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 312 (1980), S. 265-270 
    ISSN: 1432-1912
    Schlagwort(e): Phyllomedusa sauvagei ; Sauvagine ; Blood pressure ; Diuresis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. The occurrence of sauvagine, a new polypeptide from amphibian skin, and its actions on rat blood pressure and diuresis were studied. 2. Sauvagine was found to be present in the skin of all the 10 Phyllomedusa species so far studied, amounts ranging from a few micrograms to 240 μg per g fresh skin. 3. The polypeptide displayed in the rat an intense, long-lasting hypotensive action accompanied by tachycardia. Hypotension was not modified by either atropine or propranolol, excluding the participation of the autonomic nervous system in its production. Tachycardia, on the contrary, was partially inhibited by propranolol. 4. Hypotension is probably the main cause of the intense antidiuresis seen in hydrated rats following sauvagine administration. Reduction in urina volume was accompanied by a decrease in GFR and an increase in tubular Na+ reabsorption.
    Materialart: Digitale Medien
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  • 18
    Digitale Medien
    Digitale Medien
    Springer
    Journal of cancer research and clinical oncology 96 (1980), S. 281-285 
    ISSN: 1432-1335
    Schlagwort(e): Carcinogenesis ; Thyroid gland ; Rat ; NMU ; MTU
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Seventy-five female Wistar rats of 150 g each were given 3×40 mg/kg body weight nitrosomethylurea (NMU) and 4 weeks later until death (in the 9th–60th week) methylthiouracil (MTU), as a 0.1% solution in their drinking water. After 2 months, in the almost colloid-less thyroid gland individual foci appeared which consisted of sometimes colloid containing follicles with increased cytoplasmic and nuclear basophilia; they increased in number during the subsequent weeks and finally resulted in nodes with different morphologic structures. From the 16th week on there were tumors infiltrating the capsule, and after the 24th week there were angioinvasive carcinomas. Thirteen rats had developed lung metastasization after the 30th week. Cytology could only distinguish between the follicular carcinomas of low differentiation and the follicular adenomas. If these findings are applied to human pathology, one would have to reckon with adenomas which can develop their malignant characteristics without necessarily changing their histologic and cytologic appearance.
    Materialart: Digitale Medien
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 39 (1980), S. 121-124 
    ISSN: 1432-1106
    Schlagwort(e): Amygdala ; Medial preoptic nucleus ; Median eminence ; Rat ; Synaptic plasticity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Stimulation-dependent changes in synaptic effects were observed in medial preoptic nucleus neurones during stimulation of the amygdala or pyriform cortex in anaesthetized female rats. The changes occurred after 35–240 triple pulse stimuli repeated at 0.89 Hz. Median eminence stimulation did not produce any synaptic change. These data show the existence of synaptic plasticity in the neural pathway from the amygdala and pyriform cortex to the medial preoptic nucleus.
    Materialart: Digitale Medien
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  • 20
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 39 (1980), S. 241-248 
    ISSN: 1432-1106
    Schlagwort(e): Olfactory peduncle neurons ; Axonal branching ; Supernormal period ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Electrophysiological methods were employed to study the axonal properties of the neurons of anterior olfactory nucleus (AON), transition zone (TZ), and rostral prepyriform cortex (RPPC) and their projections towards the ipsilateral and contralateral olfactory bulb (IOB, COB) in the rat. Of 91 antidromically driven cells, 39 (43%) and 32 (35%) responded to IOB and COB stimulation, respectively; 20 (22%) were discharged from both bulbs. Collision tests performed on the latter group indicated that these neurons have a short main axon which divides near the soma, projecting one branch to the COB and a thinner one toward the IOB. Mean conduction velocities of axons projecting to the IOB and the COB were 0.4 m/s and 0.7 m/s, respectively, the faster conducting axons having shorter refractory periods. Of the 38 neurons tested, 92% showed decreases in threshold and latency (up to 20% of control antidromic latency) after a test volley that was preceded by a conditioning pulse at intervals of 20–215 ms. Latency decreases were greater for slowly conducting axons than for the faster ones. These after-effects of impulse activity in OB afferent axons were attributed to the presence of a supernormal period of increased conduction velocity and excitability similar to that found in the olfactory nerve (Bliss and Rosenberg, 1974).
    Materialart: Digitale Medien
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  • 21
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 40 (1980), S. 79-87 
    ISSN: 1432-1106
    Schlagwort(e): Spinal tract neuron ; Hypothalamus ; HRP ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The distribution and number of hypothalamospinal tract (HST) neurons were studied following injections of horseradish peroxidase (HRP) at various levels of the rat spinal cord. The hypothalamus was divided into four areas and one nucleus, that is, the dorsal (DHA), posterior (PHA), medial (MHA) and lateral (LHA) hypothalamic areas and the paraventricular nucleus (PVN). The total numbers of HST neurons labeled with HRP varied according to the injection levels: 6,160 (C2 injections), 3,808 (T8), 1,961 (L1), 919 (L7) and 13 (S4). With C2 injections LHA contained 3,464 neurons, which accounted for 56% of the full number of HST neurons; similarly, PVN, 1,114 (18%); MHA, 865 (14%); DHA and PHA, 817 (12%). With L7 injections, LHA contained 444 labeled neurons, which accounted for 48% of the total; PVN, 327 (36%); MHA, 71 (8%); DHA with PHA, 77 (8%). As for the rostrocaudal distribution of labeled neurons, there was only a slight difference between the C2 and L6 injections in LHA, but no difference was noticed in PVN, DHA nor PHA. The present findings suggest that 70% of HST neurons may project to the cervical and thoracic cords. Although the number of labeled HST neurons decreased as the injection sites were placed caudally, no clearcut topographical arrangement was recognized in terms of the spinal projection levels.
    Materialart: Digitale Medien
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  • 22
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 32 (1980), S. 63-68 
    ISSN: 1432-0827
    Schlagwort(e): Rat ; Bone formation ; Fluorochrome ; Microphotometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary A method for quantitative studies of the formation rate of bone has been developed. After vital staining with calcein, the fluorescence of a bone section was measured with a microphotometer controlled by a mini computer. After staining the bone structure with alizarin red S in a second step, the section was measured in transmitted light. The two data sets were combined and the shortest distances between the bone surface and the fluorescence lines were computed. With this information the distance distribution and the bone area between the label and the surface could be calculated in two different ways: with the single labeling and the continuous labeling techniques. The advantages and disadvantages of the two methods are discussed and compared with those of other techniques.
    Materialart: Digitale Medien
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 32 (1980), S. 113-122 
    ISSN: 1432-0827
    Schlagwort(e): Rat ; Bone ; Metaphysis ; Quantitative ; Aging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The purpose of this work was to analyze the proximal tibial metaphysis of the 170 g rat in a quantitative histologic fashion which would allow some relation to tissue age to be established. Stained 3 µm thick tissue sections were analyzed with the aid of a Merz grid on an eyepiece reticule and a light microscope. Tissue mass and cell distribution were studied in all areas. The rate of change in tissue mass during aging of the metaphysis was calculated. Two regions of the metaphysis were identified. One, corresponding to the primary spongiosa, less than 4.45 days of age, is a region of high turnover of hard tissue and high numbers of osteoblasts and osteoprogenitor cells. The other, corresponding to the secondary spongiosa, is a region of relatively low net tissue turnover and low numbers of osteoblasts and osteoprogenitor cells. Osteoclasts were found relatively more uniformly distributed through the metaphysis than were osteoblasts and osteoprogenitor cells. The rate of bone formation in the primary spongiosa is 50 times that found in the Haversian bone of the rib of 5-year-old humans and about 500 times that found at the cortical-endosteal surface of ribs of 5-year-old humans. It is argued that both cell distribution and tissue distribution in the metaphysis support the concept that osteoblasts and osteoclasts, rather than osteocytes, are responsible for the maturation of the metaphysis. The inhomogeneous distribution of both cells and tissue in the metaphysis has definite meaning for the interpretation of findings concerning the incorporation of radionuclides into the skeleton.
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  • 24
    ISSN: 1432-0827
    Schlagwort(e): Rat ; Hypophysectomy ; Dietary phosphorus deprivation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The demands of growth are known to exacerbate the effect of phosphorus deprivation (PD). We examined whether changes associated with PD could be prevented in young rats in which growth and growth hormone (GH) were eliminated by hypophysectomy (HPX) and whether PD in normal intact rats (INT) was associated with increased secretion of GH. INT or thyroxine- and ACTH-replaced HPX rats were fed one of the three diets: 0.31% P (NP); 0.027% P (LP), and 0.31% P, pair-fed with LP-mates (NP-PF). The results indicate that HPX did not qualitatively alter several physiologic responses to PD: (a) serum and urinary phosphorus (P) decreased and urinary calcium (Ca) increased; (b) net intestinal Ca retention fell and duodenal sac uptake of45Ca rose; and (c) external P balance was restored and duodenal sac uptake of32P-phosphate increased. Only the hypercalcemia seen in INT, LP rats was prevented by HPX. In INT rats serum immunoassayable GH levels, measured in single samples, were not different between different dietary groups while pituitary bioassayable GH was reduced in both LP and NP-PF rats when compared to the NP rats. Thus, except for hypercalcemia, the physiologic responses associated with PD are not prevented by the elimination of growth and GH, and the development of these responses in INT rats was not associated with a consistent or specific alteration in GH secretion.
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  • 25
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 43 (1980), S. 257-262 
    ISSN: 1432-0738
    Schlagwort(e): Bromobenzene ; Cytochrome P-450 ; Cytochrome reductase ; Glucuronyltransferase ; Lipoperoxidation ; Liver ; Mixed-function oxidase ; Peroxide ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In acute oral studies, the effect of bromobenzene on hepatic microsomal enzymes was investigated. Neither glucuronyltransferases nor cytochrome c reductase showed significant changes. Most of the mixed-function oxidases studied were inhibited with the exception of ketamine-N-demethylase. The data indicate that bromobenzene or its epoxide acts on cytochrome P-450 but not on all cytochrome P-450 species, and does not affect the reductase and the glucuronyltransferases. Microsomal lipoperoxidation and microsomal H2O2 formation were increased.
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  • 26
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 160 (1980), S. 239-252 
    ISSN: 1432-0568
    Schlagwort(e): Liver ; Innervation ; Adrenergic nerves ; Guinea pig ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The adrenergic innervation of rat and guinea pig liver is investigated using the glyoxylic-acid — paraformaldehyde method for fluorescent microscopical demonstration of adrenergic nerves and electron microscopy. The nerve distribution in the parenchyma of both animals is compared. The distribution of the liver nerves as detected with fluorescence microscopy is confirmed electron microscopically. The two species exhibit fundamental differences in their liver innervation: (1) In the guinea pig, a rich innervation is found in the trias as well as in the parenchyma. Many nerves traverse the entire liver lobules and may end near the central vein. The guinea pig hepatocyte innervation seems to be uniformly adrenergic. Electron microscopy shows that the varicosities of these nerves mostly form close contacts to the hepatocytes but also to other hepatic intralobular cells. (2) In the rat, the liver nerves are as a rule restricted to the triads, running mainly with smooth muscle containing blood vessels. It rarely happens that nerves penetrate into the lobule and come into contact with the peripherally located hepatocytes.
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  • 27
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 159 (1980), S. 59-69 
    ISSN: 1432-0568
    Schlagwort(e): Infrahyoid muscles ; Motoneurons ; Spinal ganglion cells ; Axons ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Perikarya of motoneurons and spinal ganglion cells attributed to infrahyoid muscle nerves of the rat were labelled by retrogradely transported horseradish peroxidase (HRP). For the differentiation of motor and sensory axons cross sections of the nerves were stained for acetylcholinesterase. Numbers and diameter distributions of perikarya and myelinated axons were determined. Motoneuronal perikarya innervating the infrahyoid muscles are located from the transition zone brain stem/spinal cord to the segment C 3. They are found mostly in the medial part of the Rexed laminae VII and VIII at the level of C 1 and C 2 and more ventrolaterally in C 3 and are therefore located to a large extent in areas until now not recognized to contain motoneurons. Our results provide evidence for a somatotopic organization of the motoneurons in the upper cervical spinal cord. The diameter distributions of motoneuronal perikarya and axons are in most cases bimodal, the two modes corresponding to α-and γ-motoneurons. In relation to the diameters of their perikarya α-axons are significantly thicker than γ-axons. In contrast to the motoneurons no clear correlation could be established between the sizes of perikarya of spinal ganglion cells and their peripheral processes.
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 160 (1980), S. 11-27 
    ISSN: 1432-0568
    Schlagwort(e): Sertoli cells ; Rat ; Fetal and postnatal life ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Sertoli cells have various functions: mechanical (creation of two compartments in the seminiferous tubules, migration of germinal cells), secretory (secretion of anti-Müllerian hormone, inhibin, androgen-binding-protein and estrogen) and phagocytic. We report an ultrastructural study of the rat Sertoli cell during maturation and consider possible correlations between the acquisition of certain morphological characteristics and certain functions. During fetal life, the Sertoli cell possesses differentiated zones of junction with the gonocytes and seems to have a role in the migration of the gonocytes towards the periphery of the seminiferous tubule. The Sertoli cell performs the phagocytosis of the gonocytes which degenerate during their migration, and seems to be the site of production of protein granules, whose presence can be related to the synthesis of anti-Müllerian hormone. After birth and before puberty, when the inclusions resembling secretory granules disappear, the Sertoli cell membranes in contact with spermatocytes II and spermatids differentiate, forming, through the differentiated junctional complexes, two compartments (adluminal and luminal) in the seminiferous tubules. Finally, they acquire the characteristics of active secretory cells, capable, in particular, of steroid synthesis.
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 158 (1980), S. 349-360 
    ISSN: 1432-0568
    Schlagwort(e): Afferent neurons ; Hypoglossal nerve ; Rat ; HRP-tracing
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Cell bodies of sensory neurons of the rat's hypoglossal nerve were demonstrated by the somatopetal horseradish peroxidase (HRP) transport technique. Labelled perikarya were found within the second and third cervical spinal ganglia and in the vagal sensory ganglia. After application of HRP to the cut peripheral trunk of the hypoglossal nerve about 200 labelled cell bodies were counted in each animal. The vast majority of the axons from cervical spinal ganglion cells reach the hypoglossal nerve via the descending ramus (N. descendens hypoglossi). However, there may exist an additional pathway, probably via the cervical sympathetic trunk. Application of HRP to the medial and lateral end branches led to a labelling of much fewer spinal ganglion cells while the number of labelled vagal sensory neurons remained unchanged. Thus, it is suggested that the majority of the cervical afferents of the hypoglossal nerve originates within the extrinsic tongue musculature and the geniohyoid muscle, whereas the vagal afferents may perhaps derive exclusively from the intrinsic muscles. Histograms of the mean diameters of labelled cell bodies show a predominance of very small perikarya. This contrasts with the diameter distribution of sensory perikarya labelled after HRP application to nerves supplying other skeletal muscles. It is therefore assumed that the afferent component of the hypoglossal nerve is composed mainly of small-calibre axons.
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  • 30
    ISSN: 1432-0428
    Schlagwort(e): Dichloroacetate ; pharmacokinetics ; lactate ; lactic acidosis ; alanine ; glucose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Dichloroacetate decreases plasma glucose, lactate, and alanine concentrations in normal and diabetic subjects, and lowers lactate concentrations and increases survival in animals with experimentally induced lactic acidosis. The relationship between these effects and plasma dichloroacetate concentrations have not been previously studied in man. Dichloroacetate (1–50 mg/kg) was infused over 30 min to 16 healthy subjects and plasma drug concentrations were followed by gas chromatography over the next 8 h. Peak plasma concentrations were linearly related to the dose (r = 0.98, p〈0.001) up to 30 mg/kg, above which 4 of 7 subjects had disproportionately high plasma drug concentrations. Nonlinear disposition was also indicated by the convex decreasing plasma elimination curves; levels declining less rapidly initially than later. At plasma concentrations below 10 μg/ml, elimination was monoexponential with a half-life of 32±11 min (mean±SD). Plasma drug clearance also decreased with doses greater than 20 mg/kg. Within 2 h of administration of the maximally effective dichloroacetate dose of 35 mg/kg, plasma lactate concentrations fell 75% below baseline and alanine fell 50% below baseline, while blood glucose was unaffected.
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 49 (1980), S. 43-49 
    ISSN: 1432-0533
    Schlagwort(e): Rat ; Peripheral nerve ; Macrophage ; Ultrastructure ; Histochemistry ; Acid phosphatase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The cellular content of the endoneurium in peripheral nerves of normal adult rats was studied. Endoneurial cells with high light-microscopical activity of acid phosphatase were usually located close to blood vessels or near the perineurium. Cells with the ultrastructural appearance of macrophages showed the same distribution and accounted for 2–4% of the endoneurial cell nuclei profiles. These cells rapidly endocytosed carbon particles after endoneurial administration of colloidal carbon in vitro.
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  • 32
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 50 (1980), S. 131-138 
    ISSN: 1432-0533
    Schlagwort(e): Rat ; Cerebellum ; Vessels ; Development
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The adult arrangement and the development of stem vessels and capillaries was studied in the rat cerebellum. In principle, stem vessels branch and terminate at three levels: (1) the molecular layer, (2) the Purkinje cell-granular layer, and (3) the cerebellar white matter. All stem vessels are interconnected by the capillary network which is most dense in the Purkinje cell—granular layer. As in the neocortex, the stem vessels of the cerebellum are formed successively during development, so that the later they are formed the more superficial are their terminations. The formation of multiple stem vessels in the depths of fissures and sulci during both pre- and postnatal development may correlate to regional variations in, e.g., mitotic frequency or thickness of the external granular layer. The earliest “endo-parenchymal” branches are formed before the first neurons are present. Capillary growth by sprouting during the postnatal period parallels known regional differences in the timing of the neuronal maturation, e.g., increased synaptic density and oxidative metabolism. The findings in this investigation confirm and extend the results of an earlier morphometric study on capillary development in the cerebellar cortex. Although the angiogenetic factors remain unknown, the hypothesis of a link between the vascularization and the functional maturation of the brain is corroborated by the results. Knowledge of the normal vascular development seems necessary for an understanding of brain morphogenesis and for interpretation of primary pathogenetic mechanisms in various intoxications etc.
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  • 33
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 50 (1980), S. 227-232 
    ISSN: 1432-0533
    Schlagwort(e): Wallerian degeneration ; Schmidt-Lantermann incisures ; Glycogen clusters ; Peripheral nerves ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Phrenic and sciatic nerves of the rat were examined during the initial stages of Wallerian degeneration 4–48 h after axotomy about 5 mm below the level of transection. One of the first changes observed in transected axons was the appearance of glycogen granules and formation of clusters of particulate glycogen at the Schmidt-Lantermann incisures and at the nodes of Ranvier. Four hours after transection, glycogen granules were found at these sites mainly attached to the tubules of axoplasmic reticulum or dispersed in small clusters in the axoplasm. At later stages, glycogen particles increased in number and formed elongated clusters arrayed mostly longitudinally among axonal organelles filling stretches of axons about 2 μm long adjacent to the incisures and in nodal regions. The buld-up of glycogen clusters reached a peak at 22 h after axotomy, when longitudinal arrays of glycogen particles were found at about 70% of the incisures and nodes examined. The percentage of these sites containing glycogen clusters had already decreased 26 h after axotomy. When axonal degeneration advanced and axons contained only floculated material and swollen mitochondria, glycogen granules also disintegrated. It is of interest that glycogen particles accumulate in those regions of the internode where the axon will soon become disrupted during ovoid formation. The possible mechanisms leading to glycogen accumulation at these sites are discussed in relation to the active role of Schwann cells in Wallerian degeneration.
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  • 34
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 50 (1980), S. 221-226 
    ISSN: 1432-0533
    Schlagwort(e): Rat ; Brain ; Vessels ; Prenatal ; Development ; Protein deprivation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The internal vascularization of the brain was studied in foetuses of normal and protein-deprived rats from embryonic day (E) 12 to 15. The position of vascular branches showed distinct relations to the various zones of the neuroepithelium. The possibility that various parts of the vascular system may differ in function, maturation, and morphogenetic relations to the neuroepithelium must be considered. The distinct vascular layers were therefore given names relating them to the respective wall zone. The ingrowth of straight stem vessels from the epiparenchymal vascular plexus into the neuroepithelium and the formation of vascular branches close to the ventricular system were referred to as stage I of the internal vascularization. The resulting plexus was called the deep vascular plexus of the ventricular zone. Its formation followed the same temporospatial gradients as the formation of the marginal zone. Following the formation of the intermediate zone, more stem vessels entered the neuroepithelium and a superficial vascular plexus of the ventricular zone was formed (stage II). This plexus was positioned close to the border between the ventricular zone and the intermediate zone. Subsequently, vascular branches also formed plexuses of the intermediate and subventricular zones (stage III). No “intraepithelial” vessels were seen on E 12. The temporospatial gradients in the telencephalic vesicles were caudal to rostral and lateral to medial, starting in the parts corresponding to the ganglionic eminence in the floor of the lateral ventricle on E 13. Only the dorsomedial angles of the hemispheres showed no vessels on E 15. No obvious differences were seen between the normal and the protein-deprived foetuses regarding the timing and extent of vascularization or the size and appearance of wall zones in the immature central nervous (I-CNS).
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  • 35
    ISSN: 1432-0827
    Schlagwort(e): Rat ; Calvarium ; Electron microscopy ; Preosteoclasts ; Osteoclasts
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary This is a study of the fine structure of cells of the 20-day fetal rat calvarium. Special attention is given to identifying and characterizing preosteoclasts. These cells are relatively common and located largely, but not exclusively, at the endocranial bone surface. The preosteoclasts are characterized by abundant mitochondria, an incomplete perinuclear Golgi apparatus, and variable-shaped dense granules. The dense granules are unique in appearance in that they contain an internal dense matrix surrounded by a clear halo. Most granules are circular in shape but some are elongate or tubular in form. Granules with identical appearance are observed in osteoclasts. The preosteoclasts are mononucleate, or occasionally binucleate. It is suggested that because preosteoclasts are morphologically distinctive and relatively abundant, it should be feasible to separate these cells from a heterogeneous cell isolate.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 45-50 
    ISSN: 1432-1041
    Schlagwort(e): ketobemidone ; narcotic analgesic ; N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The basic pharmacokinetics and oral bioavailability of ketobemidone have been studied in 6 patients after surgery. Plasma concentrations were first determined following intravenous administration of Ketogin® 2 ml, containing ketobemidone chloride 10 mg and the spasmolytic N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride 50 mg, and then, on the second postoperative day, following oral administration of 2 tablets of Ketogin®, each containing ketobemidone chloride 5 mg and the spasmolytic agent 25 mg. The average oral bioavailability of ketobemidone was 34%±16% (SD, n=6). The mean plasma half-life of elimination (t1/2β) was about the same following oral (2.45±0.73 h; SD, n=5) as after intravenous administration (2.25±0.35 h; SD, n=6). The low oral bioavailability and rapid elimination of ketobemidone demonstrated in this study suggest that the usual dosage recommendation for oral Ketogin® (ketobemidone 5–10 mg every 6–7 h) in patients with severe pain is too low.
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  • 37
    ISSN: 1432-1041
    Schlagwort(e): sodium valproate ; epileptic patients ; pharmacokinetics ; plasma concentration ; prediction ; maintenance dosage
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pharmacokinetic analysis of the plasma valproic acid concentration-time course, following a single oral dose (600 mg) of sodium valproate, was performed in 20 epileptic patients as an aid to the prediction of a proper chronic dosage regimen. A simple one-compartment model was found inadequate to describe the drug concentration-time course in 15 of the 20 patients studied. The average elimination (β phase) half-life of 9 h was shorter than that previously reported in healthy subjects. The latter observation and the wide variation in plasma valproic acid clearance observed between patients (0.09–0.53 ml/kg/min) may have been related to its altered disposition by concomitant anticonvulsant therapy. Sodium valproate maintenance therapy, determined by single-dose pharmacokinetic prediction of steady-state plasma valproic acid levels, did not require dosage adjustment because of unwanted effects. However, the occurrence of drug-related adverse events led to dosage reduction in 4 of 9 patients whose chronic therapy was not pharmacokinetically predicted. Moreover, the pharmacokinetic variability demonstrated for sodium valproate by patients on multiple therapy, whose chronic sodium valproate therapy was pharmacokinetically predicted, indicates the value of monitoring plasma valproic acid levels for the regulation of anticonvulsant therapy.
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  • 38
    ISSN: 1432-1041
    Schlagwort(e): prenalterol ; beta1-adrenoceptor agonist ; metabolic effects ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The metabolic and haemodynamic effects of three intravenous doses (0.5, 1.0 and 4.0 mg) of prenalterol, a selective β1-adrenoceptor agonist, were studied in 10 healthy male subjects. Plasma levels of prenalterol during the experiments were related to the haemodynamic effects. Prenalterol induced a dose-dependent increase in systolic blood pressure and heart rate. The maximal effects amounted to about 30 mm Hg and 15 beats/min, respectively, after the highest dose (4.0 mg). The diastolic blood pressure fell by a maximum of about 15 mm Hg. The effect of prenalterol on systolic blood pressure and heart rate persisted for about 3 h after the end of the last infusion, whereas that on diastolic blood pressure only lasted for 60 min. Compared with placebo, there was a moderate increase in plasma FFA and glycerol. A small rise in insulin level was also recorded, but no significant change was seen in other metabolic variables — triglycerides, glucose, lactate, pyruvate. Serum potassium tended to decrease and serum sodium was unchanged. The initial distribution of prenalterol was rapid (half-life 7 min) and the overall elimination rate corresponded to a plasma half-life of 2 h. A linear relationship was found between the plasma level of prenalterol and its effects on systolic blood pressure and heart rate.
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  • 39
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 189-196 
    ISSN: 1432-1041
    Schlagwort(e): flunitrazepam ; prolonged administration ; pharmacokinetics ; clinical observations ; sleep parameters
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eight patients were given flunitrazepam 2 mg orally, once daily for 28 consecutive days. The time-course of the plasma concentration of unchanged flunitrazepam and its principal metabolites were studied in detail after the first and last doses. Additional blood samples were collected immediately before administration of the tablet on days 4, 7, 11, 14, 18, 21 and 25. Clinically there were no changes during the trial period in the onset of sleep, duration of sleep, depth of sleep measured as number of spontaneous awakenings, or in the patients' condition on awakening. The time-course of the plasma concentration of flunitrazepam could be described by a three-compartment model, assuming that the rate constants remained unchanged during treatment. Maximal plasma concentrations of unchanged flunitrazepam, found two hours after intake, reached 10–15 ng/ml after the first and 15–20 ng/ml after the last dose. The β-half-life was found to be between 20 and 36 h.
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  • 40
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 209-213 
    ISSN: 1432-1041
    Schlagwort(e): disopyramide ; bioavailability ; controlled-release tablets ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentrations and bioavailability of disopyramide following repeated administration of standard capsules and controlled-release tablets have been compared. Ten patients were randomized into two groups; Group I received disopyramide capsules 150 mg every 6 h for five days and subsequently disopyramide controlled-release tablets 300 mg every 12 h for further five days. Group II received the same preparations in the reverse order. There was a more rapid rise in disopyramide concentration after the capsules: the maximum of 10.7±0.6 µmol/l (mean ± SEM) was reached within 1.8±0.4 h as compared to 10.6±0.4 µmol/l within 4.0±0.3 h after the controlled-release tablets. No significant difference in the fluctuations in individual plasma concentrations during each dose interval at steady state were observed after ordinary capsules compared to controlled-release tablets. The extent of bioavailability was the same. Eight patients reported some side-effects during the capsule period and nine during the controlled-release tablet period.
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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 215-221 
    ISSN: 1432-1041
    Schlagwort(e): L-dopa ; elderly ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Previous studies have suggested that the absorption of L-dopa in the elderly Parkinsonian patient might be unusually efficient. In the present investigation, the systemic availability of L-dopa was examined in 5 elderly Parkinsonian patients (mean age=77 years) and 6 young, healthy volunteers (mean age=26 years) following a single oral 300 mg dose of L-dopa. Quantitation of plasma levels of intact L-dopa was effected by ion-exchange column chromatography and spectrofluorimetry. The L-dopa plasma concentration-time profiles obtained confirmed the considerable intersubject variability in the absorption of L-dopa previously reported in the literature. Maximum plasma concentrations of L-dopa generally occurred within 60 min of administration of the dose. The existence of more than one plasma peak of L-dopa concentration was displayed in 45% of the subjects studied. This characteristic was not confined exclusively to either subject group. There was a significantly larger (P〈0.02) area under the plasma L-dopa concentration-time curve (AUC o ∞ ) in the elderly Parkinsonian patients (mean=234.69 µg · min/ml; SD=84.70) compared to the young, healthy volunteers (mean=82.33 µg · min/ml; SD=31.00). A significant (P〈0.01) correlation existed between AUC o ∞ and age (r=0.7970; n=11) among the subjects studied. The apparent elimination phase plasma half-life of L-dopa in the elderly Parkinsonian patients (mean=66.0 min; SD=11.1) was not significantly different to that observed in the young, healthy volunteers (mean=74.0 min; SD=18.1). These results suggest that there may be an age-related alteration to the disposition of orally administered L-dopa in the elderly Parkinsonian patient.
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  • 42
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 425-428 
    ISSN: 1432-1041
    Schlagwort(e): prazosin ; congestive heart failure ; pharmacokinetics ; oral dose ; comparison with healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of prazosin (Minipress®) were studied in nine patients with NYHA Class 3 or 4 congestive heart failure and in five healthy controls. After a single 5 mg oral dose, plasma concentrations of prazosin, as reflected in the area under the plasma concentration-time curve (AUC) and prazosin plasma half-life, were approximately double in the patients in comparison to the control group. Reduction in hepatic blood flow, altered gastrointestinal absorption of the drug or diminished intrinsic hepatic metabolic activity in the patient group may have contributed to the observed changes in prazosin disposition. The finding of higher prazosin plasma concentrations in patients with refractory heart failure demonstrates the need for close monitoring of these individuals following administration of the drug in the treatment of chronic congestive heart failure.
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  • 43
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 25-30 
    ISSN: 1432-1041
    Schlagwort(e): pethidine ; norpethidine ; placental transfer ; pharmacokinetics ; newborns
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The literature data available on pethidine and norpethidine kinetics in women in labour and in their newborns is reviewed and compared with recent personal observations. In pregnant women the apparent blood half-life of pethidine is not different from that in healthy controls, however, apparent volume of distribution and total body clearance are reduced. Norpethidine blood levels are measurable after 10–20 min and tend to increase with time. The amount of drug transferred to the foetus is clearly linked to the dose administered to the mother, the dosing-delivery interval and to the metabolic capability of the mother. An equilibrium between maternal and umbilical venous blood is reached 2–3 h after dosing for pethidine and later for norpethidine. In the neonate, the apparent pethidine half-life is 2 to 7 times longer than in adults with values ranging from 7 to 32 h. Norpethidine is actively formed in the newborn with peak blood levels at 12–36 h and an apparent blood half-life of 20–36 h. At the doses usually recommended blood concentrations at birth are frequently higher than those required for analgesia and close to or within toxic ranges. An effort toward a more individualized dosage as well as toward a better understanding of the possible role of norpethidine with regard to adverse effects is needed.
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 109-116 
    ISSN: 1432-1041
    Schlagwort(e): diuretics ; antihypertensive agents ; renal disease ; dispositon ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacodynamic actions and disposition of diuretic and antihypertensive agents may be significantly modified in subjects with renal disease. Most studies on this question have dealt with alterations in the elimination kinetics of these drugs and, while they generate descriptive data, minimal insight about changes in dose-response relationships or mechanisms of drug action are provided by such investigations. Several basic principles which may serve as useful guidelines in determining how renal failure will influence the response to drugs have been considered. They include the following: degree of renal malfunction, intrinsic toxicity of the drug, alternative pathways for drug metabolism and elimination, elimination pharmacokinetics and dose-response characteristics. Several classes of diuretic agents (thiazides, furosemide) and antihypertensive drugs (hydralazine, methyldopa, propranolol, prazosin, and clonidine) have been used as models to define how basic knowledge of renal and non-renal pathways for elimination of drugs and their pharmacodynamic actions may assist in establishing rational therapeutic regimens for these agents in patients with renal failure.
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 517-520 
    ISSN: 1432-1041
    Schlagwort(e): desmethyldiazepam ; oxazepam ; cimetidine ; hepatic elimination ; pharmacokinetics ; interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of single oral doses of desmethyldiazepam 20 mg or oxazepam 50 mg were studied in 5 healthy volunteers under controlled conditions, before and following a 24 h pretreatment with cimetidine 200 mg×5. Cimetidine significantly impaired (p=0.03) the elimination of desmethyldiazepam, as shown prolongation of its elimination half-life from 51.7±21.9 h to 72.6±39.4 h (mean ± SD), and a decrease in total plasma clearance from 12.0±2.7 ml/min to 8.6±3.3 ml/min. The disposition of oxazepam was not affected. From these results, and recently published data on diazepam and chlordiazepoxide, it is concluded that cimetidine impairs the hepatic elimination of those benzodiazepines which are metabolized by phase I reactions.
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 385-391 
    ISSN: 1432-1041
    Schlagwort(e): sulpiride ; pharmacokinetics ; serum clearance ; renal clearance ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of sulpiride was studied in 6 healthy volunteers after intravenous and oral (tablets) administration of 100 mg. An open two- and in two subjects a three-compartment model was applied following intravenous administration. The average total distribution volume during the terminal slope was 2.72±0.66 l/kg and total systemic clearance was 415±84 ml/min. The serum half-life of the terminal slope following intravenous administration averaged 5.3 h (range 3.7–7.1 h) according to the two-compartment model. In two subjects the half-lives were 11.0 and 13.9 h when the three-compartment model was applied. Determination of urinary excretion rates of unchanged sulpiride indicated a half-life of 7.15 h. Following intravenous administration, 70±9% of the dose was recovered unchanged in urine within 36 h; the mean renal clearance was 310±91 ml/min. Sulpiride was absorbed slowly, with peak concentrations appearing between 3 and 6 h after oral administration. The recovery of unchanged drug in urine following oral administration was 15±5% of the dose, with a mean renal clearance of 223±47 ml/min. The bioavailability determined from combined plasma and urine data was only 27±9%. The low bioavailability was probably due to incomplete absorption.
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 449-457 
    ISSN: 1432-1041
    Schlagwort(e): alcuronium ; single dose ; multiple dose ; plasma levels ; neuromuscular response ; pharmacokinetics ; anaesthesia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic behaviour of alcuronium is described for nineteen patients undergoing anaesthesia for elective surgery. Eleven patients received a single bolus intravenous dose of 0.25 mg/kg, while 8 patients required additional doses of 0.125 mg/kg. A two-compartment open model was found to describe adequately both the single dose and multiple dose data for the majority of patients. No significant differences were found in the model-independent pharmacokinetic parameters between the single and multiple dose studies. Mean values for the pooled data for the half-life (t1/2β), apparent volume of distribution (Vdβ), volume of distribution at steady-state (Vdss), volume of the central compartment (Vc) and plasma clearance (Clp) were 198.75 min, 24.261, 20.891, 8.181 and 90.22 ml/min respectively. Evoked muscle twitch response was monitored in 17 of the patients to assess the degree of relaxant blockade. The bolus dose of alcuronium produced complete block in 9 patients and between 95 and 99% block in the remainder. The time of onset to maximum block ranged from 3 to 30 min with the concurrently measured plasma levels of alcuronium being 0.79 to 2.25 µg/ml. The time taken following bolus administration to 5% recovery (95% paralysis) was a mean of 42 min and the corresponding mean alcuronium plasma concentration was 0.78 µg/ml.
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  • 48
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 69-74 
    ISSN: 1432-1041
    Schlagwort(e): digoxin ; neonates ; infants ; pharmacokinetics ; dosage schedules
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary As a therapeutic principle, a disease should be treated with the lowest effective dose of a drug. Accumulating information indicates that satisfactory contractile response of the myocardium is produced in young paediatric patients by doses of digoxin below existing recommendations. In addition, toxicity appears to be more frequent in neonates and infants treated with digoxin than previously thought. Therefore, dose calculations have been performed, based on pharmacokinetic parameters, with the aim of reaching and maintaining an average serum concentration of the glycoside of 2 nmol/l. This level is common in infants (〉1 month of age) during digoxin maintenance therapy and its adequacy is well supported by experience from adult cardiac patients. The calculations show that although current dosage schedules maintain the desired digoxin serum level in infants, they are often excessive for digitalization purposes. In neonates, the prevailing schemes do not sufficiently consider the immature state of the eliminating organs. Overdigitalization could therefore easily occur and continue in these patients, particularly in the premature newborns. This is in agreement with toxicity reports in the literature. The calculated doses should be less hazardous by being better adapted to the eliminating capacity of the various paediatric age-groups.
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 37-43 
    ISSN: 1432-1041
    Schlagwort(e): caffeine ; idrocilamide ; xanthine derivatives ; inhibition of metabolism ; neuropsychiatric side effects ; pharmacokinetics ; healthy man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of caffeine are greatly altered by concomitant administration of idrocilamide. In four healthy volunteers id rocilamide inhibited the biotransformation of caffeine and increased its half-life nine times. The untoward neuropsychiatric effects of idrocilamide are the consequence of abnormal accumulation of caffeine in regular consumers of caffeine-containing foods and beverages.
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 171-174 
    ISSN: 1432-1041
    Schlagwort(e): bromocriptine ; Parkinson's disease ; plasma level ; salivary level ; protein binding ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Salivary and plasma concentrations of bromocriptine (BCT), a dopamine agonist, were measured by gas chromatography in four patients with Parkinson's disease. All the patients had been on mono-therapy with BCT for years, and during the 3 weeks prior to the investigation they received constant but individually different dosage regimens. Paired samples of pure, parotid, serous saliva and of blood were collected hourly during one eight hour dose interval. The concentrations of BCT in saliva were very low and there was a ten-fold range in the areas under the salivary and plasma concentration/time curves. It is concluded that in clinical practice measurement of BCT in saliva is not suitable for exact estimation of the plasma concentration of BCT. Using the measured salivary pH and the plasma BCT concentration, calculations based on the Henderson-Hasselbalch equation showed that the assumption of about 99% plasma protein binding of BCT best fited the observed concentrations of BCT in saliva.
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 321-326 
    ISSN: 1432-1041
    Schlagwort(e): sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ten hypertensive patients with moderate to severe impairment of renal function were treated with sotalol for 5 to 10 weeks (average 6.4 weeks). Dosage was individually titrated (range 80 to 480 mg daily). The drug was given once daily in the morning. In eight patients blood pressure was satisfactorily controlled. Higher steady-state levels were observed than have been reported after similar doses in patients with normal renal function. The apparent first-order elimination rate constant and plasma clearance were significantly correlated with glomerular filtration rate. For an anuric patient, serum half-life was calculated to be 69 h. In relation to the raised plasma levels, side effects were uncommon. Since sotalol is excreted predominantly via the kidney, therapy in patients with impaired renal function should start with a low dose and any increase in dosage should be made carefully. As the anti-hypertensive effect does not appear to be correlated with the plasma level or with tolerance, adjustment of dose should be based on clinical response.
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 83-88 
    ISSN: 1432-1041
    Schlagwort(e): patent ductus arteriosus ; indomethacin ; premature newborns ; pharmacokinetics ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A review of the published data on pharmacological closure of PDA in premature newborns shows that doses of 0.2 mg/kg indomethacin are less successful when given enterally (18 to 85% closure) than when given intravenously (88 to 90% closure). The elimination half-life is markedly prolonged in premature newborns compared to adults but there are wide differences between the patients and some discrepancies between mean values reported by various authors. The present study compares clinical and pharmacological results obtained in two groups of low birth weight infants with symptomatic PDA and treated with 0.2 mg/kg indomethacin: 7 patients treated enterally (group A) and 11 patients treated intravenously (group B). Permanent closure of the ductus was observed in 4 cases in group A and in 9 cases in group B. Transient closure was observed twice in each group. Of a total of 18 infants, 15 were saved (83%). One baby treated with indomethacin in spite of preexisting oliguria died from persistent anuria. Indomethacin plasma levels were measured by gas chromatography. The mean elimination half-life of the drug in group A (40.3±12.2 h) did not differ from that in group B (33.9±11.7 h). The apparent plasma half-life appears to be inversely correlated with gestational age (r=0.66,p〈0.05). No relationship between peak plasma levels and ductal closure was established, but a significant difference was found for area under the curve (0 to 24 h) between patients in whom a permanent closure was obtained and those in whom the closure was either transient or absent.
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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 147-150 
    ISSN: 1432-1041
    Schlagwort(e): antidepressant ; geriatric ; nortriptyline ; pharmacokinetics ; prediction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Sixteen depressed elderly patients in hospital (mean age 81 years) received a single oral dose of nortriptyline prior to commencing treatment with this drug. Plasma nortriptyline measurements after the single dose were used to calculate the plasma drug clearance and to predict the daily dose required for each patient to achieve a steady-state concentration within the suggested therapeutic range of 50–150 µg·l−1. Using these dosage regimes, the mean observed steady-state concentration showed a significant correlation with the predicted values (r=0.71, p〈0.002). All patients had steady-state concentrations within or very close to this suggested range (mean 106, range 38–157 µg·l−1). Use of the prediction test can prevent the development of toxic plasma concentrations and enhance the possibility of therapeutic success. Our findings suggest that a safe starting dose of nortriptyline for the elderly is 30 mg per day.
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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 295-299 
    ISSN: 1432-1041
    Schlagwort(e): propylthiouraci ; propranolol ; carbimazole ; methimazole ; comparative activity ; pharmacokinetics ; bioactivation ; thyroid peroxidase inhibition
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The in vitro effects of equimolar concentrations (0.1, 0.33 and 1.0 mmol/l) of carbimazole, methimazole, propylthiouracil and propranolol on thyroid peroxidase activity were studied on thyroid tissue specimens obtained from euthyroid patients undergoing parathyroidectomy. In addition, the in vivo kinetics of methimazole following single dose administration (60 mg) of carbimazole and of methimazole itself were examined in 11 healthy volunteers using high-pressure liquid chromatography to measure serum methimazole. The in vitro studies were carried out at pH 6, to avoid alkaline hydrolysis of carbimazole to methimazole. Under these conditions, methimazole strongly inhibited thyroid peroxidase. Propylthiouracil had a less pronounced inhibitory effect, and carbimazole was almost and propranolol was entirely inactive. The in vivo kinetics of methimazole showed a large interindividual variation. Within individuals, there was no significant difference in the half-life or time to peak concentration of methimazole following administration of carbimazole and methimazole, respectively. However, the peak concentration and area under the curve of methimazole were significantly greater after administration of methimazole itself than after administration of carbimazole. Assuming similar bioavailability, this difference could be related to the difference in molecular weight between carbimazole and methimazole. It appears that, in man, methimazole is the most active of antithyroid agents currently available, that carbimazole is essentially inactive per se but is bioactivated to methimazole, and that carbimazole offers neither dynamic nor kinetic advantages over methimazole.
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  • 55
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 321-328 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; hypertension ; pharmacokinetics ; plasma renin ; blood pressure effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p〈0.001) between the initial (after three doses) and final (after 〉90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively).
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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 279-283 
    ISSN: 1432-1041
    Schlagwort(e): glipizide ; diabetes ; food intake ; blood glucose ; blood insulin ; pharmacodynamics ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of a standardized breakfast on the single dose (5 mg) kinetics and effects of glipizide was examined in 9 healthy volunteers and in 14 diabetics not previously exposed to a sulfonylurea. In the volunteers, glipizide caused an increase in plasma insulin and a reduction in blood glucose both during continued fasting and when the drug was taken with the breakfast. Food intake did not influence the peak concentration, the elimination half-life or the bioavailability of the drug. However, food intake significantly delayed the absorption of glipizide by about 0.5 h. In the patients, glipizide produced a significant increase in plasma insulin and a significant diminution of the rise in blood glucose in response to the meal. Starting at breakfast and for 45 min thereafter serum glipizide concentrations were significantly higher when the drug was taken 0.5 h before the meal, than when ingested concurrently with it. With the former treatment, the increase in plasma insulin occurred earlier and the blood glucose reduction was pronouncedly greater than with the latter treatment. As the absorption of glipizide may be delayed by concurrent breakfast, this may help to explain, why the administration of glipizide 0.5 h before breakfast led to a more appropriate relation between the serum concentration of the drug and the metabolic impact of the meal, thereby promoting more appropriate insulin release and better glucose disposition than after concurrent intake of the drug and breakfast.
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 347-350 
    ISSN: 1432-1041
    Schlagwort(e): dibekacin ; renal failure ; dialysis ; pharmacokinetics ; microbiological assay ; dosage regimen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of Dibekacin were studied in 10 patients with terminal renal impairment (creatinine clearance 〈5 ml/min) undergoing haemodialysis sessions lasting 4 h. The dialyzers were either the Gambro Lundia Major 13.5 or the Ultra Flo II 1.4., and the patients were divided into two groups according to the dialyzer used. Blood flow varied between 250 and 280 ml/min and dialyzate flow between 450 and 600 ml/min. All patients received a single i. v. dose of Dibekacin 1.5 mg/kg at the beginning of the dialysis session. The concentration of the antibiotic at the input and the output of the dialyzer were determined microbiologically by a plate diffusion method usingB. subtilis as the test organism. The intravenously administered antibiotic followed an open two-compartment kinetic model. The type of dialyzer used did not influence the dialysis of Dibekacin. Haemodialysis significantly increased the elimination rate of the antibiotic with respect to the interdialysis periods. The plasma half-life in the slow disposition phase fell from 30 h in the interdialysis period to 4.0 h during dialysis sessions. From the calculated pharmacokinetic parameters, a dosage regimen for this kind of patient is proposed.
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  • 58
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 383-390 
    ISSN: 1432-1041
    Schlagwort(e): prenalterol ; oxprenolol ; haemodynamics ; pharmacokinetics ; inotropic effects ; side effects ; tolerance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Prenalterol was studied in six healthy volunteers given single oral doses of 2.5, 5 and 10 mg and placebo. It displayed a distinct positive inotropic action, manifested as a dose-related reduction of 16.5–27.2 msec in the pre-ejection period (PEPc; systolic time-intervals), and an increase of 4.2–5.9 Ω/sec2 in the Heather index (impedance cardiography). There was also a dose-related increase of 17.6–34.0 mmHg in systolic blood pressure, whereas diastolic pressure showed a slight, transient decrease, not related to the dose given. Heart rate rose by 5–12 beats/min. Stroke volume, as determined by impedance cardiography, increased by 24.2–28.5 ml at all three dose-levels. The effects of the drug developed rapidly, reaching their maximum within 30–60 min and lasting for about 4 h. The time-course of the effects corresponded to the plasma concentrations of the drug. The increases in systolic pressure and contractility were linearly correlated with the plasma concentrations (r=0.8−0.9,p〈0.001). The activity of prenalterol was also tested in the same volunteers after blockade of β-receptors with oxprenolol 80 mg. Under these conditions, oral doses of 25, 50 and 100 mg produced effects similar to or slightly less marked than those recorded after doses ten times lower in the absence of β-blockade. In a further 10 healthy volunteers, in whom tolerance to prenalterol was studied by repeated administration for 10 days of 5 mg four times daily, no change in blood chemistry, haematological parameters or urine values was found. The positive inotropic effect of a single oral dose of prenalterol 5 mg was also demonstrated by reference to the systolic time-intervals and the echocardiogram, in six patients with chronic heart failure, five of whom were digitalized. Prenalterol did not give rise to premature concentrations or other arrhythmias. The only untoward effect definitely attributable to the drug was palpitation, which was dose-related and as a rule was not unduly distressing; in one volunteer, however, the palpitations were unbearable. Prenalterol is a cardiostimulant agent with no direct effect on the peripheral circulation. On the basis of its pharmacological activity, it might well be of therapeutic benefit in all conditions in which an improvement in the pumping efficiency of the heart is required.
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  • 59
    ISSN: 1432-1041
    Schlagwort(e): ketoprofen ; pharmacokinetics ; relative bioavailability ; single doses ; repeated doses ; prediction of kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC] 0 ∞ after rectal administration of a suppository showed the minimum significant difference (p〈0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 87-92 
    ISSN: 1432-1041
    Schlagwort(e): beta-blocker ; metoprolol ; slow-release formulation ; multiple dosing ; blood pressure ; heart rate ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pharmacokinetic and pharmacodynamic profiles for metoprolol have been measured in six healthy volunteers after single and multiple dosing with 100 mg conventional formulation twice daily and 200 mg slow-release formulation once daily. Both multidose regimes produced measurable predosing plasma concentrations of metoprolol. The plasma concentrations on the eighth day were greater than predicted by the single-dose data as indicated by the comparison of the total areas under the curve for the single dose and the dosage interval areas during multiple dosing. This increase may be associated with a change in the bioavailability and/or clearance of the drug and is currently being investigated. The peak concentrations for the two regimens were comparable but the times to peak with the slow-release regimen were significantly delayed. Both regimes produced significant beta-blocking effects over 24 h during multiple dosing, the reductions in exercise heart rate at 0 and 24 h on the eighth day corresponding to more than 20% of the maximum effect. Resting pulse rates and blood pressures were affected to a similar extent by the two regimens but neither significantly altered respiratory peak flow rates. The effects during multiple dosing were generally greater than those after a single dose and appeared to follow a more consistent trend. This observation, together with those for the plasma level data on the eighth day, illustrate the importance of performing multiple-dose studies in assessing beta-blocking drugs.
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    ISSN: 1432-1041
    Schlagwort(e): zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The systemic availability of a new antidepressant, zimelidine, and of its pharmacologically active metabolite, norzimelidine, was studied in six healthy male volunteers. Three single doses of zimelidine (25 mg and 100 mg orally and 25 mg i.v.) and two single doses of norzimelidine (25 mg orally and i. v.) were given to each volunteer allowing at least seven days between administrations. Plasma concentrations of zimelidine and norzimelidine were determined in serial blood samples by HPLC. Following oral zimelidine peak plasma concentrations of the metabolite were attained about 3 h after dosing. Oral administration of norzimelidine itself resulted in a plasma concentration profile for this compound that was similar to that observed after oral zimelidine. Utilising the plasma concentration data following intravenous infusion of each compound, the elimination half-lives for zimelidine and norzimelidine were calculated to be 5.1 h (range 4.3–6.0) and 15.5 h (range 10.6–22.9) respectively. The total body clearances of the 2 compounds were similar at 0.52 l · min−1 (range 0.26–0.70) for zimelidine and 0.56 l · min−1 (range 0.28–0.83) for norzimelidine. The substantially longer elimination half-life of norzimelidine was apparently the result of a larger volume of distribution (9.4 l · kg−1; range 7.8–11.4) for this metabolite, as compared to zimelidine (3.21 · kg−1; range 1.6–4.9). The calculated bioavailability of zimelidine was 26% (range 9.1–39) after the 25 mg oral dose, and 29% (range 14–46) after the 100 mg dose. The bioavailability of norzimelidine was 66% (range 36–91). However, oral administration of zimelidine resulted in as much or more norzimelidine reaching the systemic circulation, as the oral administration of norzimelidine itself. This is important as a large part of the activity of the drug may be due to the metabolite.
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  • 62
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 263-268 
    ISSN: 1432-1041
    Schlagwort(e): naproxen ; renal insufficiency ; metabolism ; protein binding ; single dose ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of naproxen after a single oral dose of 250 mg has been studied in 8 subjects with normal renal function and 16 patients with varying degrees of chronic renal insufficiency. Unchanged naproxen and its main unconjugated metabolite, 6-0-desmethylnaproxen, were determined fluorometrically in serum. In healthy subjects the elimination half-life of naproxen was 17.7± 3.0 h (mean±SD) and it was not significantly prolonged in patients with renal failure (18.1±5.3) h. No accumulation of naproxen in serum occurred in uraemic patients. On the contrary, serum drug levels were slightly but significantly lower in patients with severe renal failure. The total body clearance and apparent volume of distribution of naproxen were significantly increased in this group of patients. Decreased binding of naproxen to serum proteins was observed in patients with renal failure. The apparent half-life of desmethylnaproxen was of the same order of magnitude as that of naproxen (18.6± 4.4 h), and was also independent of renal function. A good correlation was found between the area under the curve (AUC), the peak concentration of the metabolite and the serum creatinine concentration. These observations suggest increased metabolism and an increased apparent volume of distribution of naproxen in severe renal failure, probably caused by decreased serum protein binding of the drug. However, it is proposed that in naproxen therapy no adjustment of the dosage regimen is necessary in patients with impaired renal function.
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 419-422 
    ISSN: 1432-1041
    Schlagwort(e): alminoprofene ; antalgic ; pharmacokinetics ; single dose ; multiple doses
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary 2-(p-methylallylaminophenyl) propionic acid, alminoprofene (INN), a new antalgic drug, was administered orally to men as a single (300 mg) and multiple doses (300 mg three times daily). Plasma and urine concentrations of alminoprofene were determined by gas-liquid chromatography. After the single oral dose, the peak plasma level (36.2 to 41.5 mg/l) was reached within 0.5–1.5 h. The biological half-life ranged from 2.5 to 3.2 h. During chronic administration of alminoprofene, steady-state equilibrium quilibrium was etablished within 24 h. The urinary excretion of alminoprofene as unchanged product and as glucuronide was very important.
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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 423-428 
    ISSN: 1432-1041
    Schlagwort(e): pyridostigmine ; myasthenia gravis ; pharmacokinetics ; bioavailability ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of pyridostigmine was evaluated after intravenous injection in two healthy male volunteers and after oral administration to five subjects. Plasma concentrations of pyridostigmine were determined after ion pair extraction from plasma and analysis by gas chromatography — mass spectrometry with chemical ionization, using d6-pyridostigmine as internal standard. Degradation of pyridostigmine in vitro was compensated for by use of the deuterated internal standard and by rapid cooling and separation of plasma after blood sampling. After intravenous administration of pyridostigmine 2.5 mg the plasma elimination half-life was 1.52 h, the volume of distribution was 1.43 l/kg and the plasma clearance 0.65 l/kg × h. The pharmacokinetic constants were very similar after oral administration of pyridostigmine 120 mg; the elimination half-life was 1.78±0.24 h, the volume of distribution 1.64±0.29 l/kg and the plasma clearance was 0.66±0.22 l/kg × h. The bioavailability was calculated to be 7.6±2.4%. When pyridostigmine was taken together with food, the time to reach the peak plasma concentration was prolonged from 1.7 to 3.2 h. Bioavailability, however, was not influenced by concomitant food intake. “Steady-state” plasma concentrations of pyridostigmine were measured in myasthenic patients on their ordinary dose schedule of cholinesterase inhibitor drugs. More than a seven-fold difference in steady-state plasma concentration was found between patients taking approximately the same daily dose of pyridostigmine.
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  • 65
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 473-477 
    ISSN: 1432-1041
    Schlagwort(e): aminophylline ; asthma ; serum theophylline ; pharmacokinetics ; prediction of serum level
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 15 acutely ill asthmatics the steady-state serum theophylline concentration was predicted by the method of Chiou et al. using two serum concentration measurements obtained 1 and 5h after starting a continuous infusion of aminophylline. Two theophylline assays with different precision characteristics were compared. With a precise HPLC-assay the prediction was excellent: prediction error (predicted minus measured concentration)=−0.22±1.97 mg/l (mean ± SD); r=0.922. When the theophylline concentration was determined by a rapid enzyme immunoassay of lower precision, but convenient for clinical use, the prediction was less accurate (prediction error=0.58±3.88, r=0.852). However, it was still clearly superior to dosing recommendations based on the population average of theophylline clearance, even after taking into consideration the effect of smoking, congestive heart failure and cirrhosis (prediction error=3.62±13.36, r=0.560). As employed in this study, the method may be useful in helping the physician to choose the optimal dose in severely ill asthmatics.
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 505-509 
    ISSN: 1432-1041
    Schlagwort(e): cefadroxil ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of Cefadroxil have been studied in a crossover study involving 20 experiments in four healthy volunteers (19–24 years), after oral administration of five individual doses of 250, 500, 750, 1000 and 1500 mg of the antibiotic in capsules to each person. Plasma and urine concentrations of the antibiotic were determined microbiologically by a plate diffusion method. The antibiotic followed an open, single-compartment kinetic model. The plasma half-life was not significantly influenced by dose; the average was 1.438±0.220 h. The percentage of the antibiotic excreted in urine, too, was not significantly affected by the dose, being close to 80% of the quantity originally administered within 24 h. The values of Cmax and (AUC) increased linearly with the administered dose.
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  • 67
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 237-244 
    ISSN: 1432-1041
    Schlagwort(e): isosorbide dinitrate ; 2-isosorbide mononitrate ; 5-isosorbide mononitrate ; digital plethysmography ; hypotension ; bradycardia ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary 18 subjects were given isosorbide dinitrate (ISDN) 5 mg sublingually and serum concentrations of ISDN, 2-isosorbide mononitrate (2-ISMN) and 5-isosorbide mononitrate (5-ISMN) were measured, as well as changes in digital plethysmographic amplitude, heart rate, ECG, blood pressure and Schellong's test. ISDN was rapidly absorbed and metabolized, having an elimination half-life of 29 min. Its metabolites 2-ISMN and 5-ISMN had longer half-lives of 1.75 and 7.6 h respectively. The amplitude of the α-wave of the digital plethysmograph did not change significantly either in the predrug period or after placebo administration. It increased within 4 min of administration of ISDN, and reached a maximum after 14 min; the effect lasted for about 2 h. ISDN lowers blood pressure and increases heart rate in most volunteers, but in 3 of the 18 subjects severe hypotension occurred, accompanied by severe, reversible bradycardia, which was probably due to vagal reflexes initiated by the markedly diminished ventricular enddiastolic volume (LVEDV) and pressure (LVEDP). No correlation could be demonstrated between the serum concentration of ISDN and/or its vasoactive metabolites and changes in plethysmographic amplitude.
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 391-394 
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by its peripheral beta-adrenergic blocking properties.
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 129-133 
    ISSN: 1432-1041
    Schlagwort(e): dapsone ; salivary drug elimination ; pharmacokinetics ; acetylator phenotype
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A high performance thin layer chromatographic assay for dapsone is described with a minimum level of detection of 20 ng ml−1 which is suitable for the study of dapsone pharmacokinetics in plasma and saliva. 100 mg dapsone was administered orally to seven normal adult volunteers, the mean plasma pharmacokinetic parameters were: α=0.23 h−1; β=0.0236 h−1, and t1/2β=30.2 h. Dapsone is also eliminated into the saliva and the t1/2 may be determined via its estimation in saliva. It is 73% bound to plasma protein and the saliva/plasma concentration ratio was found to be 27%. In two subjects the free plasma dapsone concentration was identical to the simultaneous salivary dapsone concentration. Therefore the salivary dapsone concentration is a measure of the free plasma fraction of dapsone. Saliva/plasma dapsone concentration ratios show no time or concentration dependence and little inter-individual variation but are unsuitable for acetylator phenotype determination because monoacetyldapsone is not eliminated in the saliva.
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  • 70
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 275-284 
    ISSN: 1432-1041
    Schlagwort(e): chlormethiazole ; cirrhosis of the liver ; antipyrine ; protein binding ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of chlormethiazole after oral and intravenous administration was studied in six healthy volunteers and eight patients with alcoholic cirrhosis of the liver. Plasma concentration-time curve after the intravenous infusion could adequately be described by two- or three-compartment open models both in healthy volunteers and in the patients. Based on the areas under the plasma concentration-time curves, the systemic bioavailability of oral chlormethiazole was about ten times greater in the patients than in healthy controls. The elimination of chlormethiazole was relatively less retarded in the patients, as indicated by a decrease of about 30% in its plasma clearance. In the patients the plasma protein binding of chlormethiazole was decreased, but the volume of distribution and half-life of elimination were unchanged. The increase in bioavailability of chlormethiazole was associated with significant alteration in the serum levels of bilirubin, albumin, alkaline phosphatase, prothrombin-proconvertin activity (P + P) and elimination rate of antipyrine or14C-aminopyrine. The increased bioavailability of oral chlormethiazole was due to impaired first-pass metabolism in the cirrhotic liver. A considerable reduction in dose seems to be indicated if oral chlormethiazole is used in patients with advanced cirrhosis of the liver. A substantial fraction of dose, averaging 15%, was lost during the intravenous infusion, presumably due to adsorption to the infusion tubing.
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  • 71
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 355-360 
    ISSN: 1432-1041
    Schlagwort(e): cis (Z)-flupentixol ; cis (Z)-flupentixol decanoate ; serum concentration ; biological half-life ; pharmacokinetics ; first-pass metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Serum concentrations of cis (Z)-flupentixol have been estimated in three male human volunteers who received cis (Z)-flupentixol by intravenous infusion, flupentixol (cis (Z)/trans (E) mixture, 1:1) orally as single and repeated doses, and i. m. cis (Z)-flupentixol decanoate in Viscoleo®. The intravenous data show that cis (Z)-flupentixol followed a multicompartment model, but it was not possible to fit the data to a two or three compartment model. The concentration curves after oral administration indicated relatively slow absorption with a peak concentration at 3–6 h, except for one case with peak at 1 h. The variation in the dosage interval after one daily oral administration was relatively limited (1.7–3.0 times), which indicates that 24 h is a reasonable dosage interval. Biological half-lives were estimated in different ways and showed some intra-individual variation; the half-life was of medium length (19–39 h). The serum concentrations after intramuscular injection of cis (Z)-flupentixol decanoate clearly demonstrated a depot effect, with a maximal concentration at 3–5 days after injection. The descending part of the serum curves allowed an approximate estimation of half-life of 3–8 days. This was not the elimination half-life, but in all probability the half-life of release of drug from the oil depot which was the rate-limiting step. From the areas under the serum concentration curves the fraction of orally administered cis (Z)-flupentixol available to the organism was calculated to be 55% (range 48–60%). The loss of drug might have been due to imcomplete absorption, but it is more likely that cis (Z)-flupentixol underwent first-pass metabolism in the gut wall and the liver. As the tablets contained about 50% cis (Z)-flupentixol, while the depot preparation contained 74% cis (Z)-flupentixol, the pharmacokinetically equivalent doses are: 10 mg tablet daily corresponds to 25 mg depot weekly. Calculation of systemic clearance gave values of 0.44–0.49 l/min, and an apparent volume of distribution was 12.5–17.2 l/kg.
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  • 72
    ISSN: 1432-1041
    Schlagwort(e): atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50–70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation.
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  • 73
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 175-183 
    ISSN: 1432-1041
    Schlagwort(e): amoxycillin ; pharmacokinetics ; bedrest ; sleep ; ambulation ; renal clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of amoxycillin in normal male volunteers was studied during the states of bedrest, sleep and ambulation. The absorption and disposition of amoxycillin in ambulatory subjects was found to be comparable to that reported previously by other workers. Serum amoxycillin concentrations were found to be significantly greater during ambulation than during bedrest and sleep. The difference in serum levels resulted from an increased apparent total serum clearance and amoxycillin renal clearance during bedrest and sleep compared to ambulation. No significant differences in the clearance was found between the states of bedrest and sleep. The change in renal clearance of amoxycillin during ambulation was attributed to a diminished renal blood flow. Although the terminal half-life of amoxycillin did not differ significantly, the apparent volume of distribution appears to be much greater during bedrest and sleep than during ambulation. This difference could be explained pharmacokinetically using a two compartment model. No significant difference was found between the rates of absorption of amoxycillin as reflected by the lag time and time to peak serum amoxycillin. The actual values for these parameters would suggest, however, that the absorption of amoxycillin is faster during ambulation than in bedrest and that the absorption rate during sleep is slowest. The clinical implications of the effect of posture and sleep on the pharmacokinetics of amoxycillin are discussed.
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  • 74
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 269-273 
    ISSN: 1432-1041
    Schlagwort(e): paracetamol ; thyrotoxicosis ; hypothyroidism ; drug disposition ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absorption, distribution and elimination of oral paracetamol have been studied in patients before and after treatment of thyrotoxicosis (n=7) and hypothyroidism (n=4). Absorption was faster in patients with untreated thyrotoxicosis than when subsequently euthyroid. The peak paracetamol concentration, however, was lower in thyrotoxic patients due to an apparent increase in the total body clearance and a shorter plasma half-life. Both absorption and elimination rates were reduced in hypothyroid patients, but were not significantly different from the euthyroid results. When estimated using a two compartment model the total volume of distribution and the hybrid distribution rate constants were unrelated to thyroid status, but the apparent volume of the central compartment was significantly greater in the thyrotoxic group. These changes in drug disposition may contribute to differences in drug response seen in thyroid disease.
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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 339-348 
    ISSN: 1432-1041
    Schlagwort(e): acebutolol ; renal failure ; dialysis ; pharmacokinetics ; N-acetylmetabolite
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of acebutolol was studied in 10 healthy subjects with normal renal function (RN), in 13 patients with various degrees of renal failure (RI) and in 8 patients undergoing repeated haemodialysis (RD). A highly specific method was used to measure acebutolol (A) and N-acetylmetabolite (NAM). In RN the decrease in plasma levels was biexponential with an apparent plasma half lives in the slow phase of A: 8.8±2.3 h and NAM: 11.4±2.2 h. The percentage of the dose excreted unchanged was 13.9% and as NAM 25.8%. Renal clearances were A: 167±20 ml/min and NAM: 150±18 ml/min. The apparent plasma half life of acebutolol does not change according to the degree of renal insufficiency (RI: 7.0±2.7 h, RD: 7.5±2.7 h), while that of NAM is increased (RI: 21.5±10.1 h, RD: 32.3±16.8 h). There is a linear relationship between the apparent elimination rate constant of NAM and creatinine clearance (r=0.832,p〈0.001). In RI 21.7% of the dose is excreted in urine (A 5.0%, NAM 16.7%). When renal function is impaired, the renal clearance of A and NAM decrease in parallel with the creatinine clearance (A: r=0.874,p〈0.001; NAM: r=0.954,p〈0.001). During dialysis the plasma half life fell (A=3.4±0.9 h, NAM=7.4±2.6 h). The dialytic clearance was A: 42.6±12.7 ml/min and NAM: 40.4±16.3 ml/min, for a blood flow of 238±35 ml/min through a dialyser with a cuprophane membrane (Ultraflo II Travenol). Acebutolol is taken up by erythrocytes (λbc=0.50±0.04). The results suggest that the dosage of acebutolol should be adjusted according to the degree of renal insufficiency.
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  • 76
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 379-384 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; aminophylline ; obstructive lung disease ; microcrystalline ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1−1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.
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  • 77
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 459-463 
    ISSN: 1432-1041
    Schlagwort(e): colestipol ; fenofibrate ; fenofibric acid ; pharmacokinetics ; interaction ; volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The possibility of a pharmacokinetic interaction between two hypolipidemic drugs, colestipol, an ion exchange resin, and fenofibrate, a phenoxyacid derivative, was studied in 6 male volunteers. The investigation followed a four-step protocol during 18 days, and relied on determination of plasma and urinary levels of fenofibric acid, the active metabolite of fenofibrate. The kinetics of a single dose of fenofibrate 300 mg was established over 3 days. Thereafter, from Days 4 to 9 fenofibrate was given daily as 200 mg in the morning and 100 mg in the evening; the plasma fenofibric acid level reached about 10 µg/ml. From Days 9 to 15 the same dose of fenofibrate was administered together with colestipol 10 g in the morning and 5 g in the evening. Plasma fenofibric acid concentrations remained unchanged and the 24 h urinary excretion of fenofibric acid did not fall. On Day 15, a last single dose of fenofibrate 300 mg was given with colestipol 15 g. The pharmacokinetic pattern of fenofibric acid on Days 15 to 18 did not differ significantly from that found previously (Days 1 to 3). From these results, it is likely that there is no pharmacokinetic interaction between the two hypolipidemic drugs.
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 51-53 
    ISSN: 1432-1041
    Schlagwort(e): pethidine ; phenobarbital ; aminoglycoside antibiotics ; pharmacokinetics ; clinical response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
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  • 79
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 55-63 
    ISSN: 1432-1041
    Schlagwort(e): diuretics ; furosemide ; caffeine ; theophylline ; neonate ; pharmacokinetics ; disposition
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The elimination of diuretics and methylxanthines is considerably slower in the neonate than in the adult. Dose guidelines, especially during long term maintenance, must be adjusted to account for this slower drug elimination. Pharmacokinetic studies and the requisite pharmacologic evaluation on diuretics such as hydrochlorothiazide, spironolactone, ethacrynic acid and others should be done. Furosemide undergoes biotransformation in the newborn producing an acid metabolite and a glucuronide conjugate. Methylxanthines are effective in the treatment of neonatal apnea. Plasma elimination of theophylline is exceedingly slow, more so with caffeine. Decreased elimination is partly explained by decreased oxidative biotransformation. Caffeine is excreted in the urine of the newborn mainly unchanged (85%) in contrast to the adult where caffeine is a minor portion of urinary excretion (2%). Theophylline is methylated to caffeine and may possibly exert additive pharmacologic effects.
    Materialart: Digitale Medien
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  • 80
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 195-198 
    ISSN: 1432-1041
    Schlagwort(e): ampicillin ; age ; oral dose ; i. v. dose ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ampicillin (500 mg) was administered intravenously (i. v.) and orally to a small panel of young and elderly subjects in a cross-over fashion. Plasma concentrations of ampicillin were measured by a fluorimetric technique for 8 h following dosage. A two compartment-open model was used to characterise the plasma concentration-time data for the intravenous study, and a one compartment-open model incorporating an absorption lag time and a first-order absorption rate constant for the oral data. Plasma clearance after i. v. ampicillin was found to be significantly decreased in the elderly (P〈0.05, 0.08 1 h−1kg−1 versus 0.18 1 h−1kg−1), and half life and area under the plasma level-time curve were significantly increased (P〈0.05, 6.70 h versus 1.68 h, t1/2β; p〈0.01, 176.51 µg·h ml−1 versus 37.88 µg·h ml−1, AUC o ∞ ) as compared to the young. No sigificant differences were observed between the age groups for the volume of distribution terms and the changes in drug handling noted in the elderly were attributed to a decrease in the renal elimination of ampicillin. Following oral administration a significant increase in t1/2β, AUC o ∞ and the maximum plasma concentration (Cpmax P〈0.01, 6.59 µg ml−1 versus 3.42 µg ml−1) of ampicillin was found in the elderly subjects. These findings were similarly attributed to a decrease in drug elimination in the aged, since no apparent age differences were noted in the pharmacokinetic parameters governing both rate and extent of ampicillin absorption.
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  • 81
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 43 (1980), S. 155-161 
    ISSN: 1432-0738
    Schlagwort(e): 1α,25-dihydroxycholecalciferol ; Calcification ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The oral administration for 5 days of excess 1α,25-dihydroxychole-calciferol [1,25(OH)2D3] at doses of 1, 5, and 25 μg/kg to rats, beginning at the age of 2 or 10 days, produced dose-dependent reductions in weight development and additional calcification near the skeleton. Alizarin red S stained skeleton revealed calcific deposits near the bones of the head, near the neural arches, between the ribs, along the bones both of the fore limbs and, to a lesser extent, of the hind limbs. Historically, the deposits appeared to be localized primarily in the subepithelial connective tissues. Starting treatment with 1,25(OH)2D3 (25 μg/kg for 5 days) at the age of 20 days produced additional calcification in 1 of 8 rats at only 1 location (lower jaw). Additional calcification as described above could no longer be induced by 1,25(OH)2D3 in 30-day-old rats using doses up to 25 μg/kg and 10 daily treatments. We conclude that the sensitivity of young rats to 1,25(OH)2D3-induced additional calcification, which differs in localization from that observed in adult rats, decreases with the maturation of the animals.
    Materialart: Digitale Medien
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  • 82
    ISSN: 1432-0738
    Schlagwort(e): Pesticides ; DNA repair ; Human lymphocytes ; Man ; Rat thymocytes ; Rat ; DNA synthesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The action of seventeen pesticides (insecticides, fungicides and herbicides) has been studied with short-term in vitro system using rat thymocytes and/or human lymphocytes. The parameters studied were: a) the action of chemicals tested in scalar doses on DNA synthesis of rat thymocytes; b) damage exerted by pesticides on human lymphocyte DNA measured as unscheduled DNA synthesis; c) the interference of chemicals tested with human lymphocyte repair capability after damage exerted on cells by ultraviolet rays. The results obtained suggest that some of tested pesticides don't induce damages to human lymphocyte DNA, some others elicit low DNA repair if compared to the repair following a standard ultraviolet irradiation and some of them (6/17) exert a marked inhibition of cell repair processes after ultraviolet irradiation. Data are discussed on the basis of a possible role played by these substances as carcinogenic agents in the environment.
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  • 83
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 45 (1980), S. 207-211 
    ISSN: 1432-0738
    Schlagwort(e): Selenate ; d,l-selenomethionine ; d,l-selenocystine ; Dimethyl selenide ; Trimethylselenonium ion ; Toxicology ; Cataract ; Ontogeny ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The toxic effect of selenium compounds (sodium selenate,d,l-selenomethionine,d,l-selenocystine, dimethyl selenide, and trimethylselenonium ion) was tested in 10-day old male rats. Increasing doses of the compounds were administered an s.c. injection and control animals were not injected. All compounds tested were lethal. Eye lens cataract was induced by the administration of selenate,d,l-selenomethionine, andd,l-selenocystine, while dimethyl selenide and trimethylselenonium ion failed to cause cataract. The cataractogenic effect of the above compounds may be attributed to their interference with glutathione metabolism.
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  • 84
    ISSN: 1432-0738
    Schlagwort(e): Methylmercury ; Inorganic mercury ; Rat ; Subcellular distribution ; Biotransformation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Accumulation of inorganic mercury in subcellular fractions of the kidney, liver, and brain of rats was studied during 48 days after a single injection of 25 mg/kg of methylmercury chloride. The highest ratio of inorganic to total mercury was seen in the cytosol of kidney, 80% of the total being as inorganic mercury at day 48. The ratio in the mitochondria and microsomes of kidney attained a maximum level (about 50% of the total as inorganic) at day 26–37. In the liver, the ratio was strikingly low in the cytosol and microsomes as compared to the light and heavy mitochondria where about 40% of the total was present as inorganic maximally at day 26. The ratio in the brain, determined up to day 15, was very low as compared with the kidney and liver, showing less than 3% of the total in the mitochondria, microsomes, and cytosol, and 5.4% in the myelin fraction. The high accumulation of inorganic mercury in the cytosol of kidney was closely related to metallothionein-like component, while those in the mitochondria and microsomes of kidney and in the mitochondria of liver were exclusively bound to high molecular weight proteins even after deoxycholate treatment.
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  • 85
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 38 (1980), S. 11-17 
    ISSN: 1432-1106
    Schlagwort(e): Cerebellum ; Pontine nuclei ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Microinjections of horseradish peroxidase (HRP) were made in different sublobules of the uvula (lobule IX, a, b, and c of Larsell, 1952) of the cerebellar cortex in the rat. These injections resulted in retrograde labeling of cells located in the pontine nuclei. Sublobule IXa receives a predominant input from a single column of cells situated in a dorsointermediate position in the caudal pontine nuclei. Sublobules IXb and IXc receive a pontine projection from two different columns of cells, one medial and one lateral. The location of the labeled cells in the lateral part of the caudal pons suggests a topographic projection to the subdivisions of the uvula. Sublobule IXa receives a projection from a distinct dorsointermediate region and sublobule IXb and IXc receive a projection from partially overlapping ventral regions. The cells of origin in the medial pons are organized such that more dorsally located cells project to sublobule IXc and ventrally located cells project to sublobule IXb with extensive overlap. These differential patterns of projections to the sublobules of the uvula along with other data in the literature suggest that sublobule IXa may be involved with different functional correlates than sublobules IXb and IXc.
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  • 86
    ISSN: 1432-1335
    Schlagwort(e): Gastric carcinoma ; Intestinal metaplasia ; N-Propyl-N′-nitro-N-nitrosoguanidine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Sequential studies were made on the histopathologic changes in the glandular stomach of rats induced by a weak carcinogen, N-propyl-N′-nitro-N-nitrosoguanidine (PNNG). Fiftyfour rats were given 100 μg/ml of PNNG in their drinking water for 44 weeks, and then normal tap water until the end of the experiment. Rats were killed at intervals between week 1 and week 88. No marked atrophy or ulceration of the mucosa was found between week 1 and the end of the experiment. Focal intestinal metaplasia was found in week 19 and its incidence increased during the experiment. Adenocarcinoma in situ with extreme cellular atypia was found in mucosa with a normal appearance in week 67. An adenocarcinoma invading the submucosa was found in week 69, and one invading the serosa in week 88. All these pathological lesions were found on the anal side of the pyloric region. No pathologic changes were found in the fundic region. The sequential changes of the mucosa of the glandular stomach induced by this weak gastric carcinogen, PNNG, were very different from those induced by the potent gastric carcinogen, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Gastric carcinoma induced by PNNG seems to be more similar to human gastric cancer than that induced by MNNG.
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  • 87
    ISSN: 1432-0584
    Schlagwort(e): Rat ; Thrombocytes ; Cell volume ; Electrophoretic mobility ; Haematopoiesis ; Ratten ; Thrombozyten ; Zellvolumen ; elektrophoretische ; Beweglichkeit ; Hämatopoese
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Die Volumenverteilung von Rattenthrombozyten zeigt zwischen dem 5. und dem 8. Tag nach Geburt eine deutliche Zunahme im Modalvolumen. Bei rechnerischer Analyse der Kurven konnten keine deutlichen Anhaltspunkte für zwei diskrete Thrombozytenpopulationen gefunden werden. Da sich jedoch der Anstieg des Modalvolumens mit dem Beginn der Produktion einer neuen Erythrozytenpopulation deckt, und außerdem die Thrombozytenkonzentration im Blut in dieser Zeit deutlich ansteigt, können diese Veränderungen Ausdruck der Produktion einer zweiten Thrombozytenpopulation sein. Die mittlere elektrophoretische Beweglichkeit der Rattenthrombozyten fällt in den ersten drei Wochen nach Geburt nur geringfügig ab, während die der Erythrozyten im gleichen Zeitraum signifikant anstiegt.
    Notizen: Summary The volume distribution curves of rat thrombocytes show a significant rise of the modal volume between days 5 and 8 after birth. No clear evidence for two distinct thrombocyte populations was obtained by computer analysis of the volume distribution curves. However, the increase of the modal volume of the platelets correlates with the production of a new erythrocyte population. In addition, the platelet concentration in the blood increases significantly during this time. These changes could indicate the production of a second thrombocyte population. The mean electrophoretic mobility of rat thrombocytes decreases only slightly during the first 3 weeks after birth, while it increases for erythrocytes significantly during the same period.
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  • 88
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 384 (1980), S. 39-47 
    ISSN: 1432-2013
    Schlagwort(e): d-Glucose ; Tubular Transport ; Glomerulotubular balance ; Micropuncture ; Clearance ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract d-Glucose transport in the kidney of glucose loaded rats was investigated using clearance and micropuncture techniques. The range of plasma glucose concentration in clearance experiments was 20–140 mmol·l−1 and in micropuncture experiments 17–94 mmol·l−1. 1. During hyperglycemia, the glucose concentration in endproximal tubular fluid was elevated above that in arterial plasma. At plasma concentrations above 60 mmol l−1 intratubular glucose concentration was found to be about 1.2 times higher than in plasma. 2. At endproximal puncture sites TF/Posmol was unity throughout the investigated range of hyperglycemia. 3. Proximal tubular glucose reabsorption during hyperglycemia is close to saturation which is compatible to aK m=10.8 mmol l−1 as determined previously. 4. Passive glucose permeability does not change during hyperglycemia. The permeability constant of 2.03·10−5 cm·s−1 does not differ significantly from that during normoglycemia, 1.9·10−5 cm·s−1. 5. Single nephron glomerular filtration rate (SNGFR) and fluid reabsorption in the proximal convolution (C) were significantly correlated during hyperglycemia (r=0.78,P〈0.001). Fractional volume reabsorption during hyperglycemia was decreased to 0.36 as compared to control, but during hyperglycemia it was not affected by the magnitude of the glucose plasma concentration. 6. During hyperglycemia, proximal tubular glucose reabsorption (TG) was correlated to SNGFR (r=0.64,P〈0.001). This relation became insignificant when the influence of volume reabsorption (C) is controlled for (r=0.17,P〉0.5). However, the significance of the correlation between TG and C persists when the influence of SNGFR is held constant. 7. Calculations indicate that when glucose reabsorption was doubled, et sodium transport was increased about fourfold. 8. In hyperglycemia, renal transport rate (TG), when factored by renal glomerular filtration rate (GFR) seems to be linearly related to glucose plasma concentration. Up to endproximal puncture site 25.5% and by the entire kidney 68.2% of the tubular glucose load were reabsorbed. The difference may be attributed either to glucose transport systems which are localized distal to the proximal convoluted tubules and/or to an inhomogenity of the glucose transport in the different types of nephrons.
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  • 89
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 384 (1980), S. 93-97 
    ISSN: 1432-2013
    Schlagwort(e): Guinea pig ; Rat ; Anesthesia ; Chronic cannulation ; Blood acid-base status
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Acid-base status of arterial blood was measured in chronically cannulated, unanesthetized, unrestrained guinea pigs. Normal values were: pH=7.444±0.032,PaCO2=35.7±4.4; HCO 3 − =24.4±2.8; BE=+0.4±2.1 (n=69) andPaO2=91.9±7.3 (n=25) (Values are mean±S.D.). Induction of light anesthesia with thiopentone caused a respiratory depression (decrease inPaO2) accompanied by respiratory acidosis (increase inPaCO2 and decrease in pH) and a development of slight metabolic acidosis (decrease in base excess and standard bicarbonate). Acid base parameters of guinea pigs are compared to those obtained from rats under identical experimental conditions.
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  • 90
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 388 (1980), S. 165-168 
    ISSN: 1432-2013
    Schlagwort(e): Colon ; Water absorption ; Electrolyte absorption ; High protein diet ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Using an in vivo sac technique, net transport of water, Na, Cl and K was studied in the colon ascendens of rats fed either a high carbohydrate (HC) or high protein (HP) diet, since water intake is elevated in HP-rats. The ligated colon sacs were filled with isotonic Krebs-Henseleit solution. Net Na and Cl absorption rates related to 1 g intestinal dry weight were 46% and 30% higher in HP-rats compared with HC-rats. Net water absorption in HP-rats exceeded that in HC-rats by 115%. Therefore the ratio between net water absorption and net absorption of solutes was higher in HP-rats than in HC-rats, and thus the hypertonicity of the absorbate was lower in the HP-rats. There was a net secretion of K in both groups of rats to about the same extent. Experiments with22Na indicate that the increased net Na absorption in HP-rats was due to an increased unidirectional Na transport from the lumen to the blood side of the colon. The group difference in the ratio between net absorption of water and solutes might be a manifestation of regulatory mechanism controlling intestinal water absorption.
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  • 91
    Digitale Medien
    Digitale Medien
    Springer
    European archives of oto-rhino-laryngology and head & neck 226 (1980), S. 123-128 
    ISSN: 1434-4726
    Schlagwort(e): Organ of Corti ; Organ-specific polypeptides ; Two-dimensional polyacrylamide gel electrophoresis ; Guinea pig ; Rat ; Actin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Two polypeptides, OCP-I and OCP-II, specific to the organ of Corti of the guinea pig and the rat, were detected by two-dimensional polyacrylamide gel electrophoresis. They were neither present in other inner ear structures, nor in other organs tested. The two polypeptides constitute a substantial portion of the total protein of the organ of Corti. Both inner and outer layer of the organ of Corti contained approximately equal amounts of OCP-I and OCP-II. The molecular weights of OCP-I and OCP-II are 37,000 and 22,500 daltons, respectively. The corresponding pI values are 4.9 and 5.1, respectively. In addition, actin and tubulin were detected in both layers of the organ of Corti.
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  • 92
    Digitale Medien
    Digitale Medien
    Springer
    Research in experimental medicine 177 (1980), S. 79-84 
    ISSN: 1433-8580
    Schlagwort(e): Mesenterico-caval shunt ; Microsurgical procedure ; Patency rate ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A microsurgical technique for mesenterico-caval shunting in the rat is described. The method results in a portal blood drainage from the upper abdominal contents whereas the blood of the mesenteric vein is shunted to the inferior caval vein. Controls were undertaken after 1 and 3 weeks, either visually or radiologically. Twenty-two of 26 surviving animals showed patency of the shunt. All animals had undisturbed blood supply to the portal stump.
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  • 93
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 257-296 
    ISSN: 1573-8744
    Schlagwort(e): chemotherapy ; pharmacokinetics ; brain tumors ; modeling ; solid tumors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract It is apparent that chemotherapy against malignant brain tumors is generally ineffective. While some agents are more effective than others, none appreciably alters the clinical course of and the poor prognosis for patients with brain tumors. Even though new and more effective agents are being or will be developed, chemotherapy depends as much on the delivery of drug as it does on the drug used. Therefore, we have defined factors that we believe are of primary importance in drug delivery to brain tumors, and, using computer simulation, we have modeled the effects of these factors. In this article we discuss (a) the extent of the “breakdown” in the blood-brain barrier (BBB) that accompanies the development of malignant tumors in the brain, (b) factors that influence drug transport from tumor capillaries to tumor cells at varying distances from the capillaries, (c) the problems inherent in drug delivery from a well-vascularized tumor outward to normal brain tissue that might harbor malignant cells but that does not have leaky vessels (i.e., normal BBB), and (d) the difficulties in drug delivery from a well-perfused, highly permeable outer tumor shell to a central, poorly perfused tumor core.
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  • 94
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 633-648 
    ISSN: 1573-8744
    Schlagwort(e): compartmental analysis ; dynamic response ; identification ; linear systems ; modeling ; parameter estimation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Single input, single output experiments can result in nonunique solutions for the rate constants of a linear compartmental model used to describe the pharmacokinetics. Where a finite number of solutions exists, a priori knowledge has to be used to distinguish between the solutions. Where there is an infinite number of solutions, assumptions have to be made about the values of some rate constants in order to obtain a unique solution for the others. This paper considers such experiments and determines whether either the addition of an extra input (simultaneously with the first input) or the taking of an extra measurement would result in a unique solution. It is found that perturbing a second input can be useful, but only if the perturbation is of different shape from the first input. Measurements of drug in urine and metabolite in plasma are generally not helpful in resolving identifiability of the drug dynamic model. If a radioactive tracer is used, though, the second measurement (for example, by externally scanning the radioactivity of the liver) can prove useful, but only if the gain of the measuring device is known.
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  • 95
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 99-104 
    ISSN: 1573-8744
    Schlagwort(e): pharmacokinetics ; pharmacological effects ; two-compartment model ; tissue accumulation ; aminoglycoside antibiotics ; gentamicin ; nephrotoxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Accumulation factors for the peripheral compartment in a two-compartment open model are derived. These expressions are contrasted with some previously published statements concerning drug accumulation. The utility of the new indices of accumulation is illustrated by reference to studies of gentamicin tissue uptake and its proposed relation to nephrotoxicity.
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  • 96
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 219-228 
    ISSN: 1573-8744
    Schlagwort(e): bumetanide ; diuretics ; pharmacokinetics ; three-compartment model ; protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Disposition of [ 14C] bumetanide administered intravenously to four healthy volunteers could be described by a triexponential equation. The mean half-lives associated with each exponent were 5.9 min, 46 min, and 3.1 hr, respectively. The largest fraction of dose was eliminated during the second phase; only 17% was eliminated during the last phase. The total plasma clearance averaged 228 ml/min, with renal clearance about one-half of this value. The recovery of unchanged bumetanide in urine over 2 days was 47% of the dose, while the total recovery of radioactivity in urine averaged 82% of dose. In plasma 93% of bumetanide was bound to proteins. Thus bumetanide is rapidly eliminated by both renal and nonrenal mechanisms. The elimination kinetics resembled those described for furosemide.
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  • 97
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 363-372 
    ISSN: 1573-8744
    Schlagwort(e): bretylium ; pharmacokinetics ; healthy subjects ; antiarrhythmic ; twocompartment model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The pharmacokinetic profile of bretylium was studied in four normal male volunteers using a new sensitive EC-GC procedure for its quantitation in biological fluids. The plasma concentrations and urinary excretion rates following the constant i.v. infusion of a single 4mg/kg dose of bretylium tosylate declined biexponentially and the data were fitted to a two-compartment model with a renal and a nonrenal route of elimination. The drug had a mean half-life (t1/2β)of 7.8 hr and apparent volume of distribution (Vd,β)of 8.18 liters/kg. The renal clearance, which was 6 times that of the glomerular filtration rate, accounted for almost 84% of the total body clearance and correlated linearly with the subjects' creatinine clearance. The observed side effects of bretylium were mild and similar to those of other adrenergic blocking agents.
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  • 98
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 421-438 
    ISSN: 1573-8744
    Schlagwort(e): bufuralol ; renal failure ; pharmacokinetics ; metabolites ; renal clearance ; hepatic clearance ; first-pass metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The beta-blocking agent bufuralol is subject to first-pass metabolism and is eliminated from the body almost entirely by biotransformation. Its major metabolite in plasma (1′-hydroxy-bufuralol) is biologically active and may contribute to the pharmacological effect of the drug. The effect of renal failure on the behavior of the parent compound and three of its metabolites was studied by comparing their kinetics in normal volunteers and in patients with severe renal insufficiency. Bufuralol was given orally to all subjects (20 mg); some of the healthy volunteers also received the drug intravenously (5 mg). Renal failure was found to be associated with a marked increase of the areas under the plasma concentration-time curves of the parent compound, whereas its halflife of elimination was not markedly influenced. The behavior of 1′-hydroxy-bufuralol was consistent with a decreased renal clearance. The behavior of bufuralol in patients with renal failure was analyzed using the clearance approach. From this analysis it appears that the presystemic biotransformation of bufuralol is decreased in renal failure and that changes in systemic clearance are compensated in our patients by modifications of the volume of distribution, resulting in little net change in the halflife of elimination.
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  • 99
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 439-461 
    ISSN: 1573-8744
    Schlagwort(e): lithium ; pharmacokinetics ; physiological parameters ; cellular transport ; three-compartment model ; circadian rhythm
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The kinetics of lithium (Li +) distribution after a single dose was studied in healthy human subjects. Experiments were performed by simultaneously following changes of Li+ concentration in plasma, erythrocytes (RBC), and urine. The data were fitted by a simple but physiologically realistic model, so that extracted rate constants could be assigned to real body compartments and compared with independent measurements of cellular transport characteristics. The extracted rate constants were used to calculate steady-state cell-to-plasma Li+ ratios for RBC and for inaccessible cells (mainly muscle). In both cell types, the intracellular Li+ concentration is far below electrochemical equilibrium. This finding suggests that the Li+ countertransport efflux mechanism of RBC may be shared with muscle. We also present evidence for a circadian rhythm in Li+ excretion that parallels the daily cycle of Na+ and K+ excretion.
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  • 100
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 89 (1980), S. 784-785 
    ISSN: 1573-8221
    Schlagwort(e): lithium ; psychotropic drugs ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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