Clonazepam acetylation in fast and slow acetylators

Publisher Website
Google Scholar
Abstract
Six slow acetylators (SA) and 6 rapid acetylators (RA), as determined by sulfamethazine (SMZ) phenotyping, were each given a 2 mg oral dose of clonazepam. Urine collections (96 h) 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 < 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.