CAJ | 학술논문

目的：考察临床常与氯吡格雷合用的CYP2C19及羧酸酯酶1（CES1）的底物药物对氯吡格雷体外代谢的影响，以期为临床上氯吡格雷的合理使用提供科学依据。方法选择CYP2C19底物（奥美拉唑）和CES1底物（依那普利、奥司他韦、辛伐他汀、罗格列酮、氟西汀），通过体外人肝微粒体代谢试验研究其与氯吡格雷代谢相互作用，采用LC-MS/MS法测定微粒体酶孵育体系中氯吡格雷非活性和活性代谢产物的浓度。结果奥美拉唑显著抑制氯吡格雷活性代谢产物的生成（P＜0.05），辛伐他汀对活性及非活性代谢产物的生成均有不同程度的抑制作用，其他CES1底物对氯吡格雷活性和非活性代谢产物的产生无影响（P＞0.05）。结论奥美拉唑、辛伐他汀对氯吡格雷有不同程度的代谢抑制作用，临床上氯吡格雷与上述药物合用时可能需要考虑其相互作用。
목적：고찰림상상여록필격뢰합용적CYP2C19급최산지매1（CES1）적저물약물대록필격뢰체외대사적영향，이기위림상상록필격뢰적합리사용제공과학의거。방법선택CYP2C19저물（오미랍서）화CES1저물（의나보리、오사타위、신벌타정、라격렬동、불서정），통과체외인간미립체대사시험연구기여록필격뢰대사상호작용，채용LC-MS/MS법측정미립체매부육체계중록필격뢰비활성화활성대사산물적농도。결과오미랍서현저억제록필격뢰활성대사산물적생성（P＜0.05），신벌타정대활성급비활성대사산물적생성균유불동정도적억제작용，기타CES1저물대록필격뢰활성화비활성대사산물적산생무영향（P＞0.05）。결론오미랍서、신벌타정대록필격뢰유불동정도적대사억제작용，림상상록필격뢰여상술약물합용시가능수요고필기상호작용。
Objective To investigate the effect of CYP2C19 and carboxylesterase 1 substrate that were often used in combination with clopidogrel in clinic and provide some useful information for the rational use of clopidogrel in clinic. Methods Omeprazole, CYP2C19 substrate, was chosen, enalapril, oseltamivir, simvastatin, rosiglitazone and fluoxetine, CES1 substrates were selected, the interactions between clopidogrel and these drugs were explored in vitro using human liver microsomes. The concentrations of clopidogrel inactive and active metabolite in the incubation system were determined by a LC-MS/MS method. Results Omeprazole significantly inhibited the formation of the clopidogrel active metabolite (P<0.05). Simvastatin exhibited varying degrees of inhibition towards the generation of both inactive and active metabolite of clopidogrel, other selected substrates did not affect the production of either inactive or active metabolite of clopidogrel (P>0.05). Conclusion Omeprazole and simvastatin showed different degrees of metabolic inhibition towards clopidogrel. When clopidogrel prescribed in combination with these drugs, the interactions of them should not be ignored in clinic.