title: Pharmacokinetics of vorapaxar and its metabolite following oral administration in healthy Chinese and American subjects.
abstract: OBJECTIVE
  Vorapaxar is a proteaseactivated receptor (PAR)-1 antagonist being developed for the prevention and treatment of thrombotic vascular events. To evaluate race/ethnic differences between Caucasians and Chinese in the pharmacokinetics of vorapaxar and its active metabolite SCH 2046273 (M20) or in the metabolite/parent ratio, we conducted a cross-study comparison on pharmacokinetic data of vorapaxar and M20 obtained from two similarly designed studies: one in healthy Chinese subjects and the other in a healthy Western (United States, [U.S.]) population.
  
  
  METHODS
  The pharmacokinetic profiles of vorapaxar and M20 were characterized using open label, two treatment parallel group designs in men and women aged 18 - 45 years. Vorapaxar was administered orally as a single dose of 40 mg in Chinese subjects (n = 14) or 120 mg in U.S. subjects (n = 14), or 2.5 mg QD for 6 weeks in both studies (Chinese, n = 14; U.S., n = 23).
  
  
  RESULTS
  Vorapaxar was rapidly absorbed in both Chinese and U.S. subjects. Vorapaxar and M20 had similar elimination half-lives. The range of metabolite/parent ratios after single dose or daily administration was largely overlapped in Chinese and U.S. subjects. Steady state was attained by day 21 for vorapaxar and M20 in both race/ethnic groups. The accumulation ratios for vorapaxar and M20 during daily administration were similar in Chinese and U.S. subjects. Vorapaxar was well-tolerated in Chinese and U.S. subjects.
  
  
  CONCLUSIONS
  The pharmacokinetic profiles of vorapaxar and M20 and the metabolite/parent ratios in healthy Chinese were generally comparable to those in a healthy Western population.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Teddy
authors.initials: T
authors.lastname: Kosoglou
authors.forename: Paul
authors.initials: P
authors.lastname: Statkevich
authors.forename: Bharath
authors.initials: B
authors.lastname: Kumar
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Marissa F
authors.initials: MF
authors.lastname: Dockendorf
authors.forename: Guoqin
authors.initials: G
authors.lastname: Wang
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lowe
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Liu
authors.forename: Zaiqi
authors.initials: Z
authors.lastname: Wang
authors.forename: David L
authors.initials: DL
authors.lastname: Cutler
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010975:Platelet Aggregation Inhibitors
chemical_list: D007783:Lactones; D011725:Pyridines; C530299:vorapaxar; D010975:Platelet Aggregation Inhibitors