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Clopidogrel Pharmacodynamics and Pharmacokinetics in the Fed and Fasted State: A Randomized Crossover Study of Healthy Men
Author(s) -
Hurbin Fabrice,
Boulenc Xavier,
Daskalakis Nikki,
Farenc Christine,
Taylor Theresa,
Bonneau Damien,
LaCreta Frank,
Cheng Sue,
Sultan Eric
Publication year - 2012
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 - 10.1177/0091270011419852
Subject(s) - clopidogrel , crossover study , pharmacokinetics , pharmacodynamics , medicine , confidence interval , active metabolite , metabolite , pharmacology , platelet , placebo , myocardial infarction , alternative medicine , pathology
Clopidogrel requires CYP450‐mediated hepatic metabolism to form its active metabolite (clopi‐H4). This randomized, placebo‐controlled, crossover study was designed to characterize the effect of a high‐fat or standard breakfast on adenosine diphosphate (ADP)—induced platelet aggregation and exposure to unchanged clopidogrel and clopi‐H4 following clopidogrel (300‐mg loading dose, 75 mg/d for 4 days) in 72 healthy men. At day 5 and as assessed by liquid chromatography—tandem mass spectrometry, unchanged clopidogrel area under the concentration‐time curve from 0 to 24 hours (AUC 0–24 ) increased 3.32‐fold (90% confidence interval [CI], 2.88–3.84), and clopi‐H4 AUC 0–24 decreased nonsignificantly by 12% (90% CI, 0.82–0.94) upon administration of clopidogrel with a standard breakfast. The estimated treatment difference in maximum platelet aggregation (MPA) induced by ADP 5 μM and assessed by light transmission aggregometry was 4.7%, with the 90% CI (0.9%–8.5%) contained within the prespecified equipotency range of ±15%. The mean ± standard deviation of day 5 inhibition of platelet aggregation was 49.7% ± 17.2% and 54.0% ± 13.3% in the fed and fasted states, respectively. Despite increased unchanged clopidogrel and slightly decreased clopi‐H4 exposure following clopidogrel administration, the numerical increase in MPA in the fed versus fasted state was small and within the prespecified limit of equipotency. These findings confirm that clopidogrel can be taken with or without food.