人体内奥美拉唑立体选择性药代动力学研究  

Studies on Enantioselective Pharmacokinetics of Omeprazole in Chinese Subjects

作　　者：姜浩[1] 钟大放[1] 王爱民[1] 

机构地区：[1]沈阳药科大学药物代谢与药物动力学实验室

出　　处：《沈阳药科大学学报》1999年第1期6-9,19,共5页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金

摘　　要：研究了８名中国健康男性受试者单剂量口服奥美拉唑（ｏｍｅｐｒａｚｏｌｅ，ＯＰＺ）胶囊２０ｍｇ后（－）ＯＰＺ和（＋）ＯＰＺ在体内药代动力学的立体选择性规律．用手性固定相ＨＰＬＣ法，测定了服药后０５，１．０，１．５，２．０，３．０，４．０，６．０ｈ不同时刻血浆中（－）和（＋）对映异构体的浓度刻，绘了相应的浓度时间曲线，并求出主要药代动力学参数．结果表明，不同时刻血浆中（－）ＯＰＺ的浓度始终高于（＋）ＯＰＺ．ＯＰＺ对映异构体的ＡＵＣ及Ｃｍａｘ比值（－）／（＋）分别为（１．５８９±０．２０１）和（１．４５８±０．２２８），其药代动力学具有明显的立体选择性（Ｐ＜０．０５）．Enantioselective pharmacokinetics was investigated after a single oral dose of 20 mg(±) omeprazole(OPZ)in 8 healthy male Chinese volunteers.The plasma concentrations of OPZenantiomers were determined for 6 hours after drug intake and concentration versus time curves were drawn and pharmacokinetic parameters were calculated.Plasma concentrations of(-) enantiomer were found always greater than those of (+) enantiomer,the ratios of (-)/(+) enantiomer for AUC and C max were 1 589±0 201,1 458±0 228,respectively,which showed the metabolic enantioselectivity of OPZ.Furthermore,it was found that the inter individual AUC differences of (+) and (-) OPZ were as high as 5 15 and 8 06 times,although the volunteers all belonged to extensive metabolizers.In comparision with the reported results of the Swedish white extensive metabolizers giving the identical dosage in literature,the AUC and C max mean values of the enantiomers in Chinese subjects were lower,and so were the inter individual variabilities.Omeprazole can be used as an in vivo probe to distinguish subjects between poor and extensive metabolizers of CYP2C19 activity according to the ratios of (-)/(+) OPZ plasma concentrations after oral administration of the racemate.

关 键 词：奥美拉唑 对映异构体 药物代谢动力学 

分 类 号：R975.2[医药卫生—药品] R969.1[医药卫生—药学]