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Biomedical subjects

R Bender

Publications and source records attributed to R Bender.

At least 109 records · Page 6Linked to original sources
PubMed1979

Pharmacokinetics of single and multiple doses of clobazam in humans.

1. The pharmacokinetics of clobazam and its biotransformation product N-desmethylclobazam were investigated after single and multiple doses in normal subjects. 2. The relevant physicochemical properties of clobazam were measured and are presented. Different assay methods (radiochemical, fluorimetric and gas chromatographic) were applied and the results correlated. 3. After single doses the pharmacokinetic profile of clobazam includes time to peak levels 1--4 h after dosing, peak levels increasing linearly with the logarithm of dose, and terminal half-lives of about 18 hours. At least 87% of an oral dose is absorbed, as indicated by urinary recovery of labelled material. 4. In multiple-dose studies unchanged clobazam levelled off at minimum steady-state concentrations within one week of dosing. During 28 d of medication N-desmethylclobazam accumulated to near steady-state levels about eight times higher than those of the unchanged compound. 5. No pharmacokinetic interactions were discovered between clobazam and the antidepressant nomifensine.

Anti-Anxiety Agents↗
PubMed1977

Kinetic interaction of nomifensine with a 1, 5-benzodiazepine (clobazam).

1. Among the numerous possibilities of drug interactions, pharmacokinetic interactions may cause mutual changes in absorption, distribution, metabolism and elimination of either drug. In the present study this approach was used to investigate pertinent effects of nomifensine and clobazam. 2. Ten normal subjects participated in an intra-individual comparison of nomifensin 75 mg alone and in combination with clobazam 15 and 30 mg. The study design was carried out according to a Latin square in double-blind conditions. One-week wash-out periods were used between the trial days. Serum levels of nomifensine were measured by radioimmunoassay (RIA) and of original clobazam by gas chromatography (GC). Classical criteria for bioavailability (peak serum levels, time of peak, area under the serum level time curve) and the half-life of elimination from the serum were used for retrieval of pharmacokinetic information. 3. Results showed no relevant differences in the criteria mentioned above, after administration of each drug alone or in combination. Therefore, extrapolations were made to multiple dose kinetics based on assumptions derived from practical therapy. They showed comprehensive agreement with therapeutic results in depressed patients. 4. The use of the classical criteria for bioavailability, in addition to the calculation of the half-time of elimination from serum, provides sufficient information for the decision whether pharmacokinetic drug interaction is present or absent. There was no such interaction after single doses of nomifensine or clobazam.

Adult↗