No differences in the pharmacodynamics and pharmacokinetics of the thrombin receptor antagonist vorapaxar between healthy Japanese and Caucasian subjects

• DOI: 10.1007/s00228-011-1127-z
• Publication Date: 2011-10-03T08:34:47Z
• Authors: Teddy Kosoglou; Larisa Reyderman; Claudia Kasserra; Lisa K. Jennings; Sophia Young; Fengjuan Xuan; Jinglan Pei; Stephen E. Maxwell; James Schiller; Alan G. Meehan; David L. Cutler
• Keywords: Adult; Male; Adolescent; Platelet Aggregation; Pyridines; Middle Aged; White People; 3. Good health; Lactones; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Asian People; Humans; Female; Receptor, PAR-1; Platelet Aggregation Inhibitors

Vorapaxar, a novel antiplatelet agent in advanced clinical development for the prevention and treatment of atherothrombotic disease, is a potent, orally bioavailable thrombin receptor antagonist selective for the protease-activated receptor 1 (PAR-1).Since race/ethnicity may affect the safety, efficacy and dosage of drugs, this study was conducted to evaluate potential differences in the pharmacodynamics, pharmacokinetics and safety of vorapaxar after single (5, 10, 20, or 40 mg) or multiple (0.5, 1, or 2.5 mg once daily) doses in healthy Japanese and matched (gender, age, height, and weight) Caucasian volunteers.Vorapaxar was well tolerated in both Japanese and Caucasian subjects. Pharmacodynamic and pharmacokinetic profiles of vorapaxar in the two racial/ethnic groups were similar. In both racial groups, complete inhibition of platelet aggregation was achieved most rapidly with vorapaxar 40 mg and was consistently achieved and maintained with a 2.5 mg daily maintenance dose.There were no substantial differences in the safety, pharmacokinetics or pharmacodynamics of vorapaxar between Japanese and Caucasian subjects.