title: Pharmacokinetics and pharmacodynamics of prasugrel in healthy Japanese subjects.
abstract: This randomized double-blind and placebo-controlled study assessed the pharmacodynamics and pharmacokinetics of prasugrel in healthy adult Japanese male subjects after single (n = 50) and multiple (n = 40) oral administration. With a single administration of prasugrel (2-30 mg), the plasma concentration of the active metabolite increased rapidly, reached a maximum at 30 min after administration, and then decreased rapidly within 4 h. The 5 mg and higher doses prevented ADP-induced platelet aggregation in a dose-dependent manner. Further analyses showed that 30 mg prasugrel exhibited the peak inhibition, and 20 mg prasugrel showed a nearly equivalent effect. With multiple doses (2.5-10 mg), the pharmacokinetic parameters on Day 1 and Day 7 were similar, and no accumulation attributable to multiple dosing was observed. The inhibitory effect on ADP-induced platelet aggregation increased with doses from 2.5 to 7.5 mg, and reached the peak level at 7.5 mg. Regarding safety, all of the drug-related adverse events observed were mild, and there were no clinically significant bleeding-related adverse events. This study indicates that a single oral administration of prasugrel at a dose of up to 30 mg and a maintenance dose of up to 10 mg are tolerated in Japanese healthy subjects.
authors.affiliation: Department of Pharmacology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu-shi, Shizuoka, 431-3192, Japan. Electronic address: umemura@hama-med.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umemura
authors.affiliation: Department of Pharmacology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu-shi, Shizuoka, 431-3192, Japan; Shin-nakagawa Hospital, 3901 Ikenoya, Izumi-ku, Yokohama-shi, Kanagawa, 245-0001, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Pharmacology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake-shi, Aichi, 470-1192, Japan.
authors.forename: Kazunao
authors.initials: K
authors.lastname: Kondo
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D007564:Japan; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D000068799:Prasugrel Hydrochloride / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D000068799:Prasugrel Hydrochloride
keywords: Inhibition of platelet aggregation; Japanese healthy subjects; P2Y(12) receptor antagonist; Pharmacokinetics; Prasugrel