Clazepam: pharmacokinetics and effects on performance.

1. The effects of clazepam, a new benzodiazepine (30 mg orally) on performance tests and the cardiovascular system have been compared to those of chlordiazepoxide (30 mg orally) and a placebo in a double-blind trial involving six healthy volunteers. Simultaneously, the pharmacokinetics of clazepam were investigated. 2. While clazepam itself could be detected neither in plasma nor in urine, it gave rise to two plasma metabolites, the former, an alcoholic derivative with a short half-life, and the second, desmethyldiazepam, with a long half-life. These two metabolites and oxazepam were excreted in urine and, within the 24 h period following drug intake, accounted for 73% of the ingested dose. 3. Seven hours after its administration, clazepam slightly improved performance and reduced anxiety. The kinetics of these effects and the metabolic data suggest that clazepam acts mainly through the formation of desmethyldiazepam. However, owing to the low blood levels of this metabolite, the activity of clazepam was very moderate.