Prasugrel, a New Thienopyridine Antiplatelet Drug, Weakly Inhibits Cytochrome P450 2B6 in Humans

Prasugrel, a thienopyridine prodrug, is hydrolyzed in vivo by esterases to a thiolactone followed by a single cytochrome P450 (CYP)‐dependent step to an active metabolite that is a potent inhibitor of adenosine diphosphate–induced platelet aggregation. This open‐label, multiple‐dose, 2‐period, fixed‐sequence study assessed CYP2B6 inhibition by prasugrel using bupropion as a probe substrate, where its active metabolite, hydroxybupropion, is almost exclusively formed by CYP2B6. Thirty healthy subjects received a single 150‐mg oral dose of sustained‐release bupropion. After a 7‐day washout, a 60‐mg prasugrel loading dose, followed by a 10‐mg daily maintenance dose for 10 days, was administered. Bupropion (150 mg) was given with prasugrel on day 7 of this phase. Prasugrel weakly inhibited CYP2B6 activity as it increased bupropion Cmax and AUC0‐∞ by 14% and 18%, respectively, and decreased hydroxybupropion Cmax and AUC0‐∞ by 32% and 23%. These results are consistent with patients receiving prasugrel not requiring dose adjustments when treated with drugs primarily metabolized by CYP2B6.