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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Different effects of clopidogrel and clarithromycin on the enantioselective pharmacokinetics of sibutramine and its active metabolites in healthy subjects
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Different effects of clopidogrel and clarithromycin on the enantioselective pharmacokinetics of sibutramine and its active metabolites in healthy subjects

机译：氯吡格雷和克拉霉素对健康受试者西布曲明及其活性代谢物的对映选择性药代动力学的不同作用

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摘要

In this study, we assessed the effects of clopidogrel and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans. Sibutramine showed enantioselective plasma profiles with consistently higher concentrations of R-enantiomers. Clopidogrel and clarithromycin significantly increased the sibutramine plasma concentration, but their effects differed between enantiomers; a 2.2-fold versus 4.1-fold increase in the AUC in S-enantiomer and 1.8-fold versus 2.0-fold for the Renantiomer, respectively. The AUCs of S- and R-desmethyl metabolites changed significantly during the clopidogrel phase (P < .001 and P < .001, respectively) but not during the clarithromycin phase (P = .099 and P = .090, respectively). Exposure to sibutramine was higher in subjects with the CYP2B6*6/*6 genotype, but no statistical difference was observed among the CYP2B6 genotypes. These results suggest that the enantioselective disposition of sibutramine and its active metabolites are influenced by the altered genetic and environmental factors of CYP2B6 and CYP3A activity in vivo.
机译：在这项研究中，我们评估了氯吡格雷和克拉霉素，分别是已知的CYP2B6和CYP3A抑制剂，对人体内外消旋西布曲明与CYP2B6多态性的对映选择性处置的影响。西布曲明显示出对映体选择性血浆分布，且R-对映体的浓度始终较高。氯吡格雷和克拉霉素显着增加了西布曲明的血浆浓度，但对映异构体的作用不同。 S-对映体的AUC分别增加了2.2倍和4.1倍，而Renantiomer的AUC分别增加了1.8倍和2.0倍。 S-和R-去甲基代谢产物的AUC在氯吡格雷阶段显着改变（分别为P <.001和P <.001），而在克拉霉素阶段则没有（分别为P = .099和P = .090）。 CYP2B6 * 6 / * 6基因型受试者的西布曲明暴露量较高，但在CYP2B6基因型之间未观察到统计学差异。这些结果表明，西布曲明及其活性代谢物的对映选择性处置受体内CYP2B6和CYP3A活性的遗传和环境因素改变的影响。

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