Comparative study of effects of vonoprazan and esomeprazole on anti-platelet function of clopidogrel or prasugrel in relation to CYP2C19 genotype.




Drug-drug interaction between anti-acid and anti-platelet agents has not been fully elucidated. Vonoprazan, a new potassium competitive acid blocker, has been available in Japan. CYP2C19 and CYP3A4 are involved in the metabolism of clopidogrel, prasugrel, esomeprazole and vonoprazan. Using P2Y12 assay, we compared the effects of vonoprazan and esomeprazole on the anti-platelet functions of clopidogrel or prasugrel in 31 healthy Japanese volunteers [14 CYP2C19 homo-extensive (homo-EMs), 9 hetero-extensive (hetero-EMs), and 8 poor metabolizers (PMs)]. Vonoprazan decreased the median inhibition of platelet aggregation (IPA) values of clopidogrel and prasugrel more potently than esomeprazole (p < 0.001 for clopidogrel and p = 0.011 for prasugrel, respectively). Same tendencies were observed when stratified by CYP2C19 genotype groups (p = 0.004 in homo-EMs, 0.033 in hetero-EMs, and 0.043 in PMs). Vonoprazan attenuated the anti-platelet function of clopidogrel more potently than esomeprazole. Esomeprazole did not affect that of prasugrel irrespective of CYP2C19 genotype. (UMIN000019901) This article is protected by copyright. All rights reserved.
PMID: 28875498 [PubMed - as supplied by publisher]
PMID: 28875498 [PubMed - as supplied by publisher]
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