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Metabolism and disposition of peptido-aminobenzophenone (2-o-chlorobenzoyl-4-chloro-N-methyl-N-glycylglycinanilide) and its major benzodiazepine metabolites in dogs.

Absorption, metabolism, and excretion of peptido-aminobenzophenone (PAB) and its major benzodiazepine-type metabolites were studied in dogs. In one dog, PAB levels reached a peak, which was low relative to that of other metabolites, at 1 hr after a single 5-mg/kg oral dose and decreased with a half-life of 1.2 hr. PAB in plasma was metabolized rapidly and extensively into chlorodiazepam (CD) and further into chlorodesmethyldiazepam (CDD). The two first-pass effects of both PAB and CD were observed. Urine following a 20-mg/kg oral dose of PAB contained the lorazepam conjugate (16.4%) as a major metabolite and a trace amount (0.2%) of PAB. The inverse relationship between CD plasma clearance and iv CD dose is probably explained by product inhibition of CD demethylation by CDD. Study of the in vitro metabolism of CD with dog liver microsomes supported the above mechanism.