氯硝西泮在快乙酰化者和慢乙酰化者中的乙酰化作用。

Clonazepam acetylation in fast and slow acetylators.

作者信息

Miller M E, Garland W A, Min B H, Ludwick B T, Ballard R H, Levy R H

出版信息

Clin Pharmacol Ther. 1981 Sep;30(3):343-7. doi: 10.1038/clpt.1981.170.

DOI:10.1038/clpt.1981.170

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.

摘要

通过磺胺二甲嘧啶（SMZ）表型分析确定的6名慢乙酰化者（SAs）和6名快乙酰化者（RAs），每人口服2毫克氯硝西泮。对这些受试者96小时的尿液收集物进行分析，检测氯硝西泮、7-氨基氯硝西泮（7-AM，氯硝西泮硝基还原代谢物）和7-乙酰氨基氯硝西泮（7-ACT，N-乙酰化的7-AM）。慢乙酰化者组比快乙酰化者组排泄更多的7-AM和更少的7-ACT；慢乙酰化者组以7-AM形式回收的平均值（±标准差）为22.7±5.0%，快乙酰化者组为13.6±4.1%，慢乙酰化者组以7-ACT形式回收的平均值（±标准差）为1.5±0.4%，快乙酰化者组为3.9±1.8%。这两个差异都很显著（经不成对t检验，p<0.02），表明氯硝西泮生物转化过程中7-AM乙酰化为7-ACT的速率由乙酰化者表型决定。