Effects of Proton Pump Inhibitors on the Antiplatelet Activity and Metabolism of Clopidogrel in Rats

OBJECTIVE To study the effects of different proton pump inhibitors(PPIs) on the antiplatelet activity and metabolism of clopidogrel in rats. METHODS Forty SD male rats were randomly divided into clopidogrel group, clopidogrel +rabeprazole group, clopidogrel+pantoprazole group, clopidogrel+lansoprazole group, and clopidogrel+omeprazole group, with 8 rats in each group. The doses of clopidogrel, rabeprazole, pantoprazole, lansoprazole, and omeprazole were 6.25, 1.8, 3.6, 2.7, 3.6 mg·kg·d^-1, respectively. Continuous administration for 7 d. The maximum platelet aggregation rate(MPA) and platelet response index(PRI) were detected by optical heterometry method and vasodilator stimulated phosphoprotein assays, respectively. The plasma concentrations of clopidogrel and its active metabolite H4 in rats were detected by LC-MS/MS. RESULTS The MPA and PRI of clopidogrel+rabeprazole group, clopidogrel+lansoprazole group, and clopidogrel+omeprazole group were significantly higher than those of clopidogrel group(P<0.05). The MPA and PRI of clopidogrel+pantoprazole group were significantly lower than those of clopidogrel+omeprazole group(P<0.05). Compared with clopidogrel group, the plasma concentrations of clopidogrel were increased and the plasma concentrations of H4 were decreased in clopidogrel+rabeprazole group, clopidogrel+lansoprazole group, and clopidogrel+omeprazole group, but the changes were not significant. CONCLUSION Rabeprazole, lansoprazole, and omeprazole attenuated the antiplatelet effect of clopidogrel. Among these PPIs, pantoprazole has the weakest inhibitory effect and omeprazole has the strongest inhibitory effect on antiplatelet effect of clopidogrel.