Kim Myong-Jin, Nafziger Anne N, Zhang Yanhua, Sellers Edward M, Gaedigk Andrea, Bertino Joseph S
Clinical Pharmacology Research Center, Bassett Healthcare, One Atwell Road, Cooperstown, NY 13326-1394, USA.
J Clin Pharmacol. 2004 Sep;44(9):966-73. doi: 10.1177/0091270004268910.
To determine if dose dependency occurs with 2 weight-based single doses of omeprazole in a phenotyping study, as well as to quantitate 3-month intraindividual variability of CYP2C19 activity, 24 Caucasian subjects with body weights from 45 to 66 kg and 67 to 90 kg received single oral 30-mg and 40-mg doses of omeprazole, respectively. Female subjects were phenotyped during the mid-follicular and mid-luteal phases of their menstrual cycles for 3 complete cycles. Male subjects were phenotyped every 14 days for 12 weeks. Subjects with a body weight between 45 and 66 kg received an additional 40-mg omeprazole single dose on visit 7. The 2-hour postdose plasma concentration ratio of omeprazole to 5-hydroxyomeprazole was used as a measure of CYP2C19 activity. The percent coefficient of variation (CV%) of omeprazole phenotyping ranged from 6.3% to 51.3% (median = 18.5%, interquartile range = 14.8%-23.5%). Weight-based single doses of omeprazole for CYP2C19 phenotyping did not exhibit dose dependency. Therefore, a weight-based approach may improve the quantitation of omeprazole/metabolites.
在一项表型研究中，为了确定基于体重的两种单剂量奥美拉唑是否存在剂量依赖性，以及定量CYP2C19活性的3个月个体内变异性，24名体重在45至66千克和67至90千克之间的白种人受试者分别接受了30毫克和40毫克的单剂量口服奥美拉唑。女性受试者在月经周期的卵泡中期和黄体中期进行表型分析，为期3个完整周期。男性受试者每14天进行一次表型分析，持续12周。体重在45至66千克之间的受试者在第7次访视时额外接受了40毫克的奥美拉唑单剂量。奥美拉唑与5-羟基奥美拉唑的给药后2小时血浆浓度比用作CYP2C19活性的指标。奥美拉唑表型分析的变异系数百分比（CV%）范围为6.3%至51.3%（中位数=18.5%，四分位间距=14.8%-23.5%）。基于体重的单剂量奥美拉唑用于CYP2C19表型分析未表现出剂量依赖性。因此，基于体重的方法可能会改善奥美拉唑/代谢物的定量。
