Kinetics of biotransformation of clonazepam to its 7-amino metabolite in the monkey.

The pharmacokinetic behavior of the 7-amino metabolite of clonazepam administered exogenously and formed endogenously from the parent drug was studied in a group of rhesus monkeys using constant rate intravenous infusions. Plasma levels of the 7-amino metabolite and/or clonazepam were determined with a GC-CI-MS method. The biological half-life of the 7-amino metabolite (2.2 +/- 1.0 hr) was shorter than that of clonazepam (4.9 +/- 0.2 hr). Total body clearance of the metabolite (0.83 +/- 0.16 liters/hr/kg) was larger than that of the parent drug (0.55 +/- 0.09 liters/hr/kg). The kinetics of in vivo biotransformation were described by a two-compartment model in which formation and disposition of the metabolite follow first-order processes. The fraction of a dose of clonazepam appearing in the systemic circulation as 7-amino metabolite was 0.70 +/- 0.30. This value may underestimate the actual fraction formed, if the metabolite is susceptible to first-pass metabolism following in situ formation.