Interaction Between Clopidogrel and Proton Pump Inhibitors: Hypothesis to Explain Multifactorial CYP2C19 Inhibition

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.