Species differences in the disposition and metabolism of camazepam

After i.v. injection of camazepam, plasma camazepan concn. declined biexponentially. The half-life of the elimination phase (t1/2, beta) increased in the order: mice (0.73 h), rats (1.3 h), dogs (5.3 h). After oral dosing of camazepam, absorption was almost complete whereas systemic availability varied eight-fold, i.e., rats and mice (10-15%) less than dogs and monkeys (about 60%) less than humans (greater than 90%), indicating species difference in the first-pass effect. Camazepam was metabolized extensively in all species investigated to more than 10 metabolites, which were desmethyl, descarbamoyl and/or hydroxy products. 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.