Clonazepam acetylation in fast and slow acetylators.
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.
D000107:Acetylation; D000284:Administration, Oral; D000328:Adult; D001570:Benzodiazepinones / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002998:Clonazepam / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010641:Phenotype; D013418:Sulfamethazine / Q000378:metabolism; D013997:Time Factors
D001570:Benzodiazepinones; D013418:Sulfamethazine; D002998:Clonazepam