Pharmacodynamic evaluation of Clopidogrel coadministered with Ilaprazole - An Open-label Randomized Controlled Trial

Clopidogrel inhibits platelet aggregation and is indicated for preventing vascular ischemia associated with atherothrombotic events. The human cytochrome P450 (P450) isoforms are involved in the two oxidative steps in the bioactivation of clopidogrel (prodrug) to its pharmacologically active metabolite. Common clinical practice involved the coadministration of a proton pump inhibitor with clopidogrel to reduce the risk of upper gastrointestinal bleeding associated with clopidogrel use. All PPIs are also metabolized via the cytochrome P450 system, particularly CYP2C19, and CYP3A4.

PPIs inhibit these isoenzymes to different degrees and therefore could affect the clinical efficacy of clopidogrel. Many studies reported an unexpected decrease in clopidogrel efficacy when co-administered with PPIs, Metabolism of clopidogrel requires cytochrome P450s (CYPs), including CYP2C19. However, PPIs may inhibit CYP2C19, potentially reducing the effectiveness of clopidogrel. Currently, researches are focused on more potent PPIs.

Some studies have shown that ilaprazole might be a new substitute. The irreversible inactivation of CYP2C19 is the mechanism by which omeprazole and esomeprazole reduce the efficacy of clopidogrel. This property is not shared by lansoprazole,

pantoprazole, rabeprazole or ilaprazole. Based on data from many pharmacokinetic and pharmacodynamic studies,  pantoprazole is the least likely to interact, and ilaprazole, lansoprazole, and rabeprazole may be a suitable alternative. There is insufficient evidence regarding which PPI among pantoprazole, ilaprazole is least likely to interact and there have been no studies to date to specifically compare the effect

of ilaprazole on clinical outcomes in patients taking clopidogrel.