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  • 1
    Electronic Resource
    Electronic Resource
    Abstracts of papers (1982)
    Springer
    Pharmacy world & science 4 (1982), S. 205-212 
    Details
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01959141
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and relative bioavailability of cyclobarbital calcium in man after oral administration (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 443-450 
    Details
    ISSN: 1432-1041
    Keywords: Cyclobarbital calcium ; pharmacokinetics ; plasma concentration ; relative bioavailability ; oral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and relative bioavailability of cyclobarbital calcium have been studied after oral administration of Phanodorm, of tablets according to the Formularium Nederlandse Apothekers (1968; FNA), and an aqueous solution. Six healthy volunteers participated in the investigation on three occasions and each received the three preparations. The dose administered was 300 mg cyclobarbital calcium. Plasma concentrations of cyclobarbital were determined at regular intervals. Absorption from the three preparations was rapid and was faster from the solution. Peak concentrations were usually attained within 1 h. The elimination of cyclobarbital could be described by a single first-order process with an average half-life of 11.6 h (range 8 – 17 h). There was little intra-subject variation of the half-life. Relative bioavailability for each volunteer was estimated by comparing the areas under the plasma concentration curves. The FNA-tablets and Phanodorm exhibited similar bioavailability, whereas the average bioavailability of the solution was 78% of that of FNA-tablets; the reason for this unexpected finding is unknown. It was concluded that cyclobarbital cannot be regarded as a uniformly suitable drug for the treatment of insomnia. The long half-life that was apparent in some of the volunteers (15 – 17 h) creates a substantial risk of residual effects on the following morning. In principle, however, the calcium salt of cyclobarbital may be used for induction of sleep, because of its rapid absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606563
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Influence of mild thyroid dysfunction on antipyrine clearance and metabolite formation in man (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 99-103 
    Details
    ISSN: 1432-1041
    Keywords: antipyrine ; thyroid dysfunction ; antipyrine metabolites ; drug metabolism ; hypothyroid patients ; hyperthyroid patients ; salivary measurements
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The salivary kinetics and rates of metabolite formation of antipyrine were studied in 6 hyperthyroid and 6 hypothyroid out-patients on 2 occasions, on admission and when T3 and T4 levels had returned to normal after treatment with carbimazole (hyperthyroidism) or l-thyroxine (hyperthyroidism). In hyperthyroidism the half-life of antipyrine was significantly shorter (p〈0.05) than after recovery (9.3±1.0 versus 10.6±0.9 h). Hypothyroid patients showed a significantly longer elimination half-life before treatment than after recovery (12.7±2.6 versus 10.3±2.6 h). Antipyrine clearance in hyperthyroid patients was decreased after treatment from 2.7±0.3 to 2.4±0.3 l/h, and it was increased in hypothyroid patients from 2.1±0.4 to 2.5±0.5 l/h (p〈0.05). The changes in clearances for the production of the antipyrine metabolites 4-hydroxyantipyrine (OHA), norantipyrine (NORA) and 3-hydroxy-methylantipyrine (HMA) were of the same order of magnitude as total antipyrine clearance, and no selectivity towards any of the metabolic pathways of antipyrine was apparent. Mild thyroid dysfunction seems to affect oxidative drug metabolizing enzyme activity in a non-selective manner and only to a small extent (10–30%). It is suggested that adjustment of the therapeutic regimens of various drugs in mild thyroid disease will only rarely by required on the basis of pharmacokinetic considerations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395214
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Nisoldipine: Kinetics and effects on blood pressure and heart rate in patients with liver cirrhosis after intravenous and oral administration (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 387-394 
    Details
    ISSN: 1432-1041
    Keywords: nisoldipine ; cirrhosis ; pharmacokinetics ; blood pressure ; heart rate ; calcium entry blocker ; concentration-effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and effects on blood pressure and heart rate of nisoldipine were studied in 8 patients with cirrhosis and in 8 age-matched healthy controls. On separate occasions each subject received nisoldipine by i.v. infusion (0.37 mg in 40 min) and as a tablet (5 mg for patients and 20 mg for control subjects). After i.v. nisoldipine, the elimination half-life was 9.7 h in control subjects and 16.6 h in the cirrhotics. The volume of distribution was 4.1 l/kg and 6.4 l/kg and the total systemic clearance was 847 ml/min and 494 ml/min, respectively. On oral nisoldipine, systemic availability was fourfold higher in patients with cirrhosis: 14.7% versus 3.7%. After i.v. administration of nisoldipine there was a brief decrease in systolic and diastolic blood pressure in both groups, whereas the heart rate increased. After 4 h a second effect peak appeared in the control subjects. After oral nisoldipine similar effect-time profiles were found, but effects lasted longer than after i.v. administration. Comparison of the maximal total plasma concentration of nisoldipine and the maximal effect in the two groups revealed that sensitivity to nisoldipine was not different in patients with cirrhosis. A reduction in the dose of nisoldipine is recommended when cirrhotics require oral nisoldipine in therapeutic practice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542441
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  • 5
    Electronic Resource
    Electronic Resource
    Influence of cimetidine on steady state concentration and metabolite formation from antipyrine infused with a rectal osmotic mini pump (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 681-684 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; antipyrine ; antipyrine kinetics ; plasma ; saliva ; antipyrine metabolism ; osmotic minipump ; rectal drug delivery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The utility of an osmotic rectal drug delivery system as a tool in steady-state pharmacokinetic interaction studies has been investigated using the cimetidine-antipyrine interaction. Antipyrine was administered to six healthy male volunteers at the rate of 15 mg/h until steady-state was reached. Cimetidine 400 mg was then given followed by 200 mg cimetidine after 2, 4 and 6 h. Antipyrine kinetics in plasma and saliva were assessed, and metabolite excretion was determined in urine. Antipyrine levels in plasma and saliva increased shortly after cimetidine administration, indicating inhibition of antipyrine metabolizing enzymes. From the metabolite data it was concluded that all major metabolic pathways of antipyrine were affected to the same extent. The effect lasted somewhat longer than anticipated on the basis of the plasma cimetidine concentrations, but it had disappeared within 48 hours after cessation of treatment. It is concluded that the osmotic rectal drug delivery system is a useful tool in pharmacokinetic interaction studies, because it provides very constant steady-state concentrations, thus permitting investigation of the time course of drug interactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607915
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  • 6
    Electronic Resource
    Electronic Resource
    Stereoselective pharmacokinetics of oral nitrendipine in elderly hypertensive patients with normal and impaired renal function (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 423-427 
    Details
    ISSN: 1432-1041
    Keywords: Nitrendipine ; enantiomers ; stereoselectivity ; Renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the enantiomers of nitrendipine has been studied in seven elderly patients with chronic renal failure (CRF) and in six control subjects (mean creatinine clearance 30 and 97 ml·min−1 respectively). Racemic nitrendipine 20 mg was given once daily for seven days and the pharmacokinetics of the enantiomers over the last dosage interval were determined using a stereospecific assay. In both groups nitrendipine exhibited stereoselective pharmacokinetics (AUC, Cmax), but the half-lives of the enantiomers did not differ in individual subjects. As an index of stereoselectivity, the mean S/R ratio of AUCs in control subjects (2.07) was not significantly different from the ratio in patients with CRF (2.68). The mean AUCs of (S)- and (R)-nitrendipine during the last dosage interval were increased in CRF by 132% and 85%, respectively. The observed doubling of the half-lives and the increases in Cmax did not reach significance because of the large variability in each group. Thus, the pharmacokinetics of oral nitrendipine is altered in CRF, but there was no change in the stereoselectivity of its pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280129
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  • 7
    Electronic Resource
    Electronic Resource
    Stereoselective pharmacokinetics of oral felodipine and nitrendipine in healthy subjects: correlation with nifedipine pharmacokinetics (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 163-169 
    Details
    ISSN: 1432-1041
    Keywords: Felodipine ; Nitrendipine ; Nifedipine ; pharmacokinetics ; stereoselectivity ; enantiomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of racemic (rac) felodipine, rac-nitrendipine and nifedipine (all given as an oral dose of 20 mg in solution) have been investigated in a randomised cross-over study in 12 healthy male subjects using stereoselective assays. Both felodipine and nitrendipine exhibited stereoselective pharmacokinetics. On average, the AUCs of the active (S)-enantiomers of felodipine and nitrendipine were 139% and 104% higher than those of their optical antipodes, but the elimination half-lives of the enantiomers of each racemate were not different. The AUCs of nifedipine, rac-felodipine, rac-nitrendipine and of their enantiomers were highly correlated (all r〉0.83), suggesting closely related rate limiting steps in the in vivo first-pass metabolism of these high-clearance drugs. Stereoselectivity was only a minor contributor to inter-individual variability in the oral pharmacokinetics of these compounds in healthy subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315475
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of butobarbital after single and multiple oral doses in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 263-271 
    Details
    ISSN: 1432-1041
    Keywords: Butobarbital ; pharmacokinetics ; plasma concentration ; oral administration ; accumulation ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method is described for the assay of therapeutic levels of butobarbital (5-ethyl-5-n-butylbarbituric acid) in human plasma, which involves a single extraction step followed by gas chromatography with alkali flame ionization detection. The pharmacokinetics of butobarbital were studied in five healthy volunteers after oral administration of 200 mg. Plasma concentrations were determined at regular intervals up to 96 h and the data were fitted by non-linear, least squares regression analysis according to one-compartment kinetics. The average lag time was 0.11 h and the absorption half-life 0.21 h. The elimination half-life varied from 33.6 to 41.5 h with an average of 37.5 h. Four of the volunteers participated in a study of multiple dosing (every 24 h) during which substantial accumulation of butobarbital was observed. The elimination half-life after termination of drug administration had decreased to about 20–25% of its initial value, probably because of enzyme induction. It was concluded that butobarbital could not be regarded as a suitable drug for treatment of insomnia, since CNS depressant effects were likely to persist into the following day. Repeated administration of butobarbital should be avoided and its incidental use restricted to patients who require day-time sedation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558339
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  • 9
    Electronic Resource
    Electronic Resource
    Stimulation of drug metabolism by rifampicin in patients with cirrhosis or cholestasis measured by increased hexobarbital and tolbutamide clearance (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 287-293 
    Details
    ISSN: 1432-1041
    Keywords: Rifampicin ; induction of drug metabolism ; cirrhosis ; cholestasis ; hexobarbital kinetics ; tolbutamide kinetics ; plasma concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients with hepatic cirrhosis or cholestasis were treated with rifampicin for 7 to 132 days. Ten patients received hexobarbital (7.32 mg/kg) and five received tolbutamide (20 mg/kg) by i.v. infusion prior to and after rifampicin treatment; plasma concentrations of the two test compounds were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 624 to 262 min and that of tolbutamide from 292 to 160 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased more than two-fold and that of tolbutamide almost two-fold. The results suggest that rifampicin is able to stimulate hepatic drug metabolism in patients with liver disease. It was apparent in general that the induction did not lead to improvement of hepatocellular function during disease as judged by laboratory findings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607679
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  • 10
    Electronic Resource
    Electronic Resource
    Influence of mild thyroid dysfunction on antipyrine clearance and metabolite formation in man (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 99-103 
    Details
    ISSN: 1432-1041
    Keywords: antipyrine ; thyroid dysfunction ; antipyrine metabolites ; drug metabolism ; hypothyroid patients ; hyperthyroid patients ; salivary measurements
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The salivary kinetics and rates of metabolite formation of antipyrine were studied in 6 hyperthyroid and 6 hypothyroid out-patients on 2 occasions, on admission and when T3 and T4 levels had returned to normal after treatment with carbimazole (hyperthyroidism) or l-thyroxine (hyperthyroidism). In hyperthyroidism the half-life of antipyrine was significantly shorter (p〈0.05) than after recovery (9.3±1.0 versus 10.6±0.9 h). Hypothyroid patients showed a significantly longer elimination half-life before treatment than after recovery (12.7±2.6 versus 10.3±2.6 h). Antipyrine clearance in hyperthyroid patients was decreased after treatment from 2.7±0.3 to 2.4±0.3 l/h, and it was increased in hypothyroid patients from 2.1±0.4 to 2.5±0.5 l/h (p〈0.05). The changes in clearances for the production of the antipyrine metabolites 4-hydroxyantipyrine (OHA), norantipyrine (NORA) and 3-hydroxy-methylantipyrine (HMA) were of the same order of magnitude as total antipyrine clearance, and no selectivity towards any of the metabolic pathways of antipyrine was apparent. Mild thyroid dysfunction seems to affect oxidative drug metabolizing enzyme activity in a non-selective manner and only to a small extent (10–30%). It is suggested that adjustment of the therapeutic regimens of various drugs in mild thyroid disease will only rarely by required on the basis of pharmacokinetic considerations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00553162
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    Paper (German National Licenses)
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