title: Pharmacokinetic and pharmacodynamic effects of prasugrel in healthy Korean males.
abstract: Prasugrel is a thienopyridine for treatment of acute coronary syndromes in patients undergoing percutaneous coronary intervention. Higher concentrations of prasugrel's active metabolite (R-138727) have been observed in Asian than white subjects. The primary objective was to investigate pharmacokinetics of R-138727 in healthy Korean males. Thirty subjects were randomized (1:2) to a 60 or 30 mg loading dose, subsequently (1:1:1) to 10-, 7.5-, or 5-mg maintenance doses. R-138727 plasma concentrations were analyzed with liquid chromatography/mass spectrometry. Platelet aggregation was measured with Accumetrics VerifyNow. Mean (coefficient of variation) exposure to R-138727 was 600 ng·h/mL (16%) after 60 mg prasugrel and 283 ng·h/mL (17%) after 30 mg. After 10, 7.5, and 5 mg, mean exposures were 78.1 (24%), 58.4 (21%), and 38.3 ng·h/mL (24%). Pharmacokinetics were linear over this range. Daily 5 mg doses maintained a 65% (SD = 14.5%) inhibition of adenosine diphosphate-induced platelet aggregation; all other doses produced ≥90%. Prasugrel was well tolerated with no serious adverse events. Results are consistent with other studies of Asian subjects administered prasugrel. Although further guidance will be provided by a recently completed phase 3 study, these preliminary data suggest that dosing strategies approved for white patients with acute coronary syndromes are applicable to Asian patients.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Park
authors.forename: Ronan P
authors.initials: RP
authors.lastname: Kelly
authors.forename: Namyi
authors.initials: N
authors.lastname: Gu
authors.forename: Christopher
authors.initials: C
authors.lastname: Payne
authors.forename: David S
authors.initials: DS
authors.lastname: Small
authors.forename: Hyunah C
authors.initials: HC
authors.lastname: Choi
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawakatsu
authors.forename: Philippe
authors.initials: P
authors.lastname: Pinton
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D001711:Biotransformation; D001792:Blood Platelets / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000068799:Prasugrel Hydrochloride; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects; D013876:Thiophenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes; D000244:Adenosine Diphosphate; D000068799:Prasugrel Hydrochloride