Inhibitory Effect of Vonoprazan on the Metabolism of [14C]Prasugrel in Human Liver Microsomes

Background and Objectives A recent report indicated that the pharmacodynamic interaction between clopidogrel and vonoprazan leading to attenuation of the anti-platelet effect of clopidogrel was unlikely to be caused by the inhibition of cytochrome P450 (CYP) 2B6, CYP2C19, or CYP3A4/5 by vonoprazan, based on in vitro CYP inhibition data. The current report investigates another important antiplatelet inhibitor, prasugrel, that is also activated through metabolism by CYP2B6, CYP2C19 and CYP3A4/5, for its CYP-based DDI potential with vonoprazan. The report describes in vitro metabolic inhibition assessments using radiolabeled prasugrel and human liver microsomes (HLMs).