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Prasugrel, a New Thienopyridine Antiplatelet Drug, Weakly Inhibits Cytochrome P450 2B6 in Humans
Author(s) -
Farid Nag A.,
Payne Christophe D.,
Ernest C. Steven,
Li Y. Grace,
Winters Kennet J.,
Salazar Danie E.,
Small Davi S.
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007309709
Subject(s) - prasugrel , thienopyridine , pharmacology , bupropion , active metabolite , prodrug , cyp2b6 , metabolite , chemistry , drug interaction , medicine , pharmacokinetics , cytochrome p450 , clopidogrel , cyp3a4 , metabolism , myocardial infarction , pathology , smoking cessation
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 C max and AUC 0‐∞ by 14% and 18%, respectively, and decreased hydroxybupropion C max and AUC 0‐∞ by 32% and 23%. These results are consistent with patients receiving prasugrel not requiring dose adjustments when treated with drugs primarily metabolized by CYP2B6.