Zhang Huixia, Ragueneau-Majlessi Isabelle, Levy Rene H
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA.
Drug Metab Lett. 2009 Dec;3(4):287-9. doi: 10.2174/187231209790218136.
Clopidogrel is an antiplatelet drug that requires bioactivation to its active metabolite to demonstrate its antiplatelet effect. Formation of the active metabolite involves multiple cytochrome P450 enzymes, with CYP2C19 playing an important role. Clopidogrel is often co-administered with proton pump inhibitors (PPIs) to decrease GI-tract bleeding, and decreased antiplatelet effect has been observed in these patients. This observation cannot be explained by the weak inhibitory effect of PPIs on CYP2C19. A hypothesis is proposed to interpret the phenomenon of PPI inhibition based in part on the finding that clopidogrel is itself an inhibitor of CYP2C19.
氯吡格雷是一种抗血小板药物，需要生物转化为其活性代谢产物才能发挥抗血小板作用。活性代谢产物的形成涉及多种细胞色素P450酶，其中CYP2C19起重要作用。氯吡格雷常与质子泵抑制剂（PPI）联合使用以减少胃肠道出血，但在这些患者中观察到抗血小板作用减弱。这一现象无法用PPI对CYP2C19的微弱抑制作用来解释。基于氯吡格雷本身是CYP2C19抑制剂这一发现，提出了一个假说来解释PPI抑制现象。
