Species differences in the disposition and metabolism of camazepam

Abstract

1. After i.v. injection of camazepam, plasma camazepan concn. declined biexponentially. The half-life of the elimination phase (t_{1/2, β}) increased in the order: mice (0.73 h), rats (1.3 h), dogs (5.3 h).

2. After oral dosing of camazepam, absorption was almost complete whereas systemic availability varied eight-fold, i.e., rats and mice (10.15%) < dogs and monkeys (about 60%) < humans (> 90%), indicating species difference in the first-pass effect.

3. Camazepam was metabolized extensively in all species investigated to more than 10 metabolites, which were desmethyl, descarbamoyl and/or hydroxy products.

4. In comparison with camazepam, plasma concn. of pharmacologically active metabolites, temazepam, oxazepan and hydroxy camazepam, were much higher in rats and mice than in dogs and monkeys.