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  • 1980-1984  (287)
  • 1905-1909
  • pharmacokinetics  (165)
  • Rat  (122)
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 331-333 
    ISSN: 1432-1041
    Schlagwort(e): ketoconazole ; vaginal candidosis ; oral antimycotic ; distribution ; pharmacokinetics ; vaginal tissue concentrations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma samples and biopsies of vaginal tissue were obtained from 23 healthy women undergoing operative sterilization, 1 to 6 h after a single oral dose of ketoconazole 200 mg. Drug concentrations in plasma and tissue, were measured by a specific gas chromatographic method. The vaginal tissue concentration averaged 2.4 times less than the corresponding plasma levels. Equilibrium between tissue, and plasma was established within 1 h after dosing, when vaginal tissue levels exceeded 1 µg/g. Ketoconazole concentrations decayed monoexponentially over the time interval studied (1–6 h), with the similar half-lives of 1.2 and 1.4 h in plasma and tissue, respectively. Following an oral 200 mg dose, a tissue concentration not less than 0.01 µg/ml was maintained over a 12 h period. This concentration has been shown to prevent outgrowth of the invasive (pseudo) mycelial form ofCandida albicans. Hence, a b.i.d. or t.i.d. dosage schedule of ketoconazole in vaginal candidosis would give continuously effective levels at the site of infection. Ketoconazole concentrations in vaginal fluid are thought to be much higher than in the tissue because of ion-trapping. The present data may explain the efficacy of oral ketoconazole in the treatment of vaginal candidosis.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-2072
    Schlagwort(e): Cyclazocine ; Acute treatment ; Dopamine ; Noradrenaline ; Serotonin ; Monoamine metabolites ; Brain regional assay ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of cyclazocine on the metabolism of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) in regions of rat brain were studied by measuring changes in the levels of the monoamines and their major metabolites. Doses ranging from 4–32 mg/kg were tested. Rats were sacrificed 1 or 2 h after administration of the drug, according to the experiment. Administration of cyclazocine significantly decreased DA concentration and increased the levels of DOPAC and HVA in striatum. Cyclazocine decreased the levels of NA, and markedly increased the levels of MHPG-SO4 and 5-HIAA in cortex, hypothalamus, midbrain and pons-medulla, while little change in 5-HT concentration, except a decrease after the highest dose, was observed. These changes in the metabolism of the monoamines differed in their amplitude and temporal nature. The possible roles of dopaminergic, noradrenergic and serotoninergic neurons in different brain regions are discussed in relation to modifications of locomotor activity and the induction of bizarre behavior resulting from cyclazocine administration in rats. These investigations may add to the understanding of the mechanism of psychotomimetic effects produced in man by this drug.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-1912
    Schlagwort(e): Guanfacine ; Clonidine ; Continuous infusion ; Withdrawal ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In conscious unrestrained spontaneously hypertensive and normotensive rats, prepared with permanently indwelling abdominal aortic catheters, the effects on blood pressure and heart rate of a 12-day continuous subcutaneous infusion of guanfacine (10 mg/kg/day) and clonidine (500 μg/kg/day) and sudden interruption of these treatments were studied. Both drugs significantly and consistently reduced the mean arterial pressure and heart rate throughout the infusion period in the SH rats, but not in the normotensive animals. The magnitude of the effects of both drugs in the SH rat were similar. Following withdrawal of treatment with guanfacine, a discontinuation syndrome was evoked, much less severe than that observed after suspension of the infusion with clonidine. The withdrawal syndromes were characterized by an overshoot of heart rate and a period of blood pressure lability. In spite of the ineffectiveness of guanfacine and clonidine to reduce blood pressure and heart rate consistently in the normotensive rat, similar withdrawal patterns as those found in the SH rat were observed. These findings are in general agreement with the results previously found in clinical studies in hypertensive patients. The spontaneously hypertensive rat may prove a suitable animal model for pre-clinical studies of discontinuation symptoms after cessation of treatment with antihypertensive drugs.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 170 (1984), S. 79-85 
    ISSN: 1432-0568
    Schlagwort(e): Perineuronal net ; Astrocytes ; Fastigial nucleus ; Cerebellum ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The morphological study of the rat fastigial nucleus with the Golgi-Rio Hortega method showed the presence of glial perineuronal nets surrounding the large neurons, but not the small ones. This perineuronal net appeared as a mesh of tenuous glial processes which covers the neuronal perikarya and proximal dendrites. The small alveolate compartments in this mesh seem to correspond to the holes for the synaptic boutons. Our results also indicate that the perineuronal net is derived from interneuronal protoplasmic and velate astrocytes. Using camera lucida drawings of this perineuronal net we have made a quantitative estimation of the size and density of synaptic boutons on these large neurons. The average numerical density of synaptic boutons was about 19 per 100 μm2 of the neuronal surface, the mean area of the synaptic holes being 2.5 μm2. Furthermore, the quantitative data evidence that about 52.5% of the neuronal surface is presumably occupied by synaptic boutons whereas the remaining 47.5% is covered by the glial processes of the perineuronal net. Semithin sections prepared from thick Golgi sections were used for the cytological study of the neurons surrounded by this glial pericellular network. The possible functional significance of the perineuronal net in the regulation of synaptic transmission in the fastigial cerebellar nucleus is briefly discussed.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1432-1041
    Schlagwort(e): amitriptyline ; imipramine ; clomipramine ; antidepressant overdose ; clinical effects ; pharmacokinetics ; cardiotoxicity ; maprotiline ; doxepine ; nortriptyline ; opipramol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24 h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 µg/l, with concentrations above 500 µg/l in 11 cases. The serum amitriptyline concentration remained high for 3–4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 µg/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidpressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60–500 µg/l) but not high (〉500 µg/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 389-392 
    ISSN: 1432-1041
    Schlagwort(e): cefoxitin ; beta-lactam antibiotics ; pharmacokinetics ; serum concentration ; pleural fluid concentration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cefoxitin was studied in 6 healthy volunteers and in 5 patients with a pleural effusion after administration of a single dose of 30 mg/kg i.v. infusion. The serum and pleural fluid concentrations of cefoxitin were determined microbiologically. The elimination half-life of the antibiotic from pleural fluid in all cases was 2–3fold longer than from serum, which shows a difference between the kinetic elimination processes of the antibiotic from the two fluids. The slow elimination of cefoxitin from pleural fluid facilitates its accumulation in this compartment during a multiple dosage regimen.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 395-398 
    ISSN: 1432-1041
    Schlagwort(e): haemofiltration ; cefoxitin ; pharmacokinetics ; renal failure ; beta-lactam-antibiotics ; haemodialysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cefoxitin was studied in patients with renal impairment during haemofiltration and in the intervening periods after administration of 30 and 15 mg/kg of the drug, respectively. Different pharmacokinetic patterns were established during haemofiltration and in the interim period, with average elimination half-lives of 11.85±4.3 and 3.41±0.6 h, respectively. The average fraction of the cefoxitin dose eliminated in haemofiltration was 0.62±0.11, more than that established in haemodialysis. In patients with terminal renal impairment undergoing haemofiltration every 48 h, a dose of 15 or 30 mg/kg is recommended at the start and at the end of each haemofiltration session.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 105-110 
    ISSN: 1432-1041
    Schlagwort(e): phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 105-110 
    ISSN: 1432-1041
    Schlagwort(e): phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 129-134 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; ethinylestradiol ; oral contraceptives ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of chronic oral contraceptive (OC) usage on the disposition of theophylline was examined. Aminophylline solution (4 mg/kg) was given orally to 8 healthy female non-OC users and to 8 healthy women who were chronic (〉6 months) OC users. The OC user group had a significantly lower total plasma clearance of theophylline than women not using OC (35.1±5.6 vs. 53.1±14.5 ml/h/kg). The t1/2 was also significantly prolonged in the OC group (9.79±1.43 vs. 7.34±1.75 h) while the volume of distribution was similar between the 2 groups. The serum ethinylestradiol (EE) concentrations after oral OC administration were measured simultaneously. The apparent clearance of EE was about 30% lower in the OC users. A significant positive correlation was found between the apparent clearance of EE and the plasma clearance of theophylline. The effects of OC are predominantly due to chronic use with decreased elimination of both theophylline and EE.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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