The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers

The dosing regimen of prasugrel adjusted for Japanese patients was compared with that of clopidogrel by analyzing the pharmacokinetics and pharmacodynamics in 40 healthy Japanese subjects in a randomized, single-blind crossover study. In period 1, the subjects received either 300 mg clopidogrel or 20 mg prasugrel; after a >2-week interval (period 2), the drug was switched. Blood samples of 36 of the 40 subjects were collected for analysis of pharmacokinetics, pharmacodynamics, and CYP2C19 genotypes. The plasma concentration of the active metabolite of prasugrel increased rapidly and reached its peak 30 minutes postadministration, whereas that of the active metabolite of clopidogrel reached its peak 1 hour postadministration. The mean AUC and Cmax of the active metabolite of clopidogrel, but not those of prasugrel, were CYP2C19 genotype dependent. Prasugrel rapidly inhibited platelet aggregation, reaching its maximum effect 1 hour postadministration. Clopidogrel, on the other hand, showed maximum inhibition 2 hours postadministration. Platelet aggregation inhibition by clopidogrel was significantly lower in the poor-metabolizer subjects than in the extensive-metabolizer subjects. Overall, prasugrel inhibited platelet aggregation more rapidly and more effectively in healthy Japanese subjects than was observed for clopidogrel.