Abstract
Six slow acetylators (SAs) and six rapid acetylators (RAs), as determined by sulfamethazine (SMZ) phenotyping, were each given a 2-mg oral dose of clonazepam. Ninety-six-hour urine collections from these subjects were analyzed for clonazepam, 7-amino clonazepam (7-AM, clonazepam nitroreduced metabolite), and 7-acetamido clonazepam (7-ACT, N-acetylated 7-AM). The SA group excreted more 7-AM and less 7-ACT than the RA group; mean (+/- Sd) recovered as 7-AM was 22.7 +/- 5.0% for the SA group and 13.6 +/- 4.1% for the RA group and mean (+/- SD) recovered as 7-ACT was 1.5 +/- 0.4% for the SA group and 3.9 +/- 1.8% for the RA group. Both differences were substantial (p less than 0.02 by unpaired t test) and indicate that the rate of acetylation of 7-AM to 7-ACT in the biotransformation of clonazepam is determined by the acetylator phenotype.
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