Details

Autor(en) / Beteiligte

• Chen, Xia
• Kosoglou, Teddy
• Statkevich, Paul
• Kumar, Bharath
• Li, Jing
• Dockendorf, Marissa F
• Wang, Guoqin
• Lowe, Robert S
• Jiang, Ji
• Liu, Hongzhong
• Wang, Zaiqi
• Cutler, David L
• Hu, Pei

Titel

Pharmacokinetics of vorapaxar and its metabolite following oral administration in healthy Chinese and American subjects

Ist Teil von

• International journal of clinical pharmacology and therapeutics, 2014-10, Vol.52 (10), p.889

Ort / Verlag

Germany

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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). 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. 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.