Abstract
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.
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This work was supported in part by NIH Research Contract No. N01-NS-1-2283 and Research Grant No. NS-04053 awarded by the National Institute of Neurological and Communicative Disorders and Strokes, PHS/OHEW.
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Lai, A.A., Min, B.H., Garland, W.A. et al. Kinetics of biotransformation of clonazepam to its 7-amino metabolite in the monkey. Journal of Pharmacokinetics and Biopharmaceutics 7, 87–95 (1979). https://doi.org/10.1007/BF01059443
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DOI: https://doi.org/10.1007/BF01059443