Platelet Aggregation Inhibitory Effects and Pharmacokinetics of Prasugrel Used in Combination With Aspirin in Healthy Japanese Subjects

Abstract

We evaluated the pharmacokinetics and pharmacodynamics of prasugrel used in combination with aspirin in healthy Japanese subjects. All subjects received aspirin 100 mg/day. Subsequently, in the single‐administration study, 23 subjects also received prasugrel 20 or 30 mg, and in the multiple‐administration study, 20 subjects received a loading dose of prasugrel 20 or 30 mg on day 1, followed by a maintenance dose of prasugrel 5 or 7.5 mg/day, respectively, on days 2–5. In both studies, the plasma concentration of the active metabolite of prasugrel, R‐138727, reached a maximum 0.5 hours after administration and rapidly decreased within 4 hours. In the single‐administration study, the inhibitory effect on adenosine diphosphate–induced platelet aggregation was significantly higher in the prasugrel 20‐ and 30‐mg groups than in the placebo group at all times (1–144 hours) after administration. In the multiple‐administration study, a similar antiplatelet effect was found after both the loading dose and the maintenance dose and was maintained for 3–6 days after the last administration. There were study drug‐related adverse events; however, all were mild, and none was clinically significant.

Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers

“…The active metabolite of vicagrel and clopidogrel has irreversible effects on P2Y12 on the platelet membrane. However, the life of circulating human platelets is only 8–10 days, and ~20% platelets are renewed daily (Umemura et al, 2017 ). After the discontinuation of the vicagrel and clopidogrel, the blood platelets will gradually back to normal in 5–8 days (DRUG LABEL INFORMATION of clopidogrel 1 ; Figure 2 ).…”