title: Safety, pharmacokinetics and pharmacodynamics of single/multiple doses of the oral, direct Factor Xa inhibitor rivaroxaban in healthy Chinese subjects.
abstract: OBJECTIVE
  To investigate the safety, pharmacokinetics and pharmacodynamics of rivaroxaban, an oral, direct Factor Xa (FXa) inhibitor, in healthy, male Chinese subjects.
  
  
  METHODS
  Two randomized, single-blind, placebo-controlled, dose-escalation studies were conducted in healthy Chinese men aged 18-45 years. In the single-dose study, subjects received single, oral doses of rivaroxaban 2.5, 5, 10, 20 and 40 mg. In the multiple-dose study, oral rivaroxaban was administered in doses of 5, 10, 20 and 30 mg twice daily for 6 days.
  
  
  RESULTS
  Rivaroxaban, in single and multiple doses up to 60 mg, was well tolerated. Rapid absorption was observed in both studies (time to C(max) 1.25-2.5 h). In the multiple-dose study, rivaroxaban exposure increased dose-proportionally after the first dose and at steady state (for the 5-20-mg doses). The half-life of rivaroxaban was up to 7.9 h in the single-dose study. Maximal inhibition of FXa activity was achieved within 1-3 h of dosing in the single-dose study [at 20 mg FXa inhibition as a median percentage change from baseline, 45.92; 95% confidence interval (CI) 44.64, 50.70] and 2-3 h after administration at steady state in the multiple-dose study (at 20 mg median FXa inhibition as a median percentage change from baseline, 60.25; 95% CI 56.16, 63.05), in line with maximum rivaroxaban plasma concentrations.
  
  
  CONCLUSIONS
  Rivaroxaban demonstrated predictable pharmacokinetics and pharmacodynamics in healthy Chinese subjects, in line with findings observed previously in White subjects. This suggests that fixed doses of rivaroxaban may be administered to all patients, regardless of their ethnic origin.
authors: Medical Department, Bayer HealthCare Company Ltd., Beijing, China.
authors: Xia
authors: X
authors: Zhao
authors: Peihong
authors: P
authors: Sun
authors: Ying
authors: Y
authors: Zhou
authors: Yuwang
authors: Y
authors: Liu
authors: Huilin
authors: H
authors: Zhang
authors: Wolfgang
authors: W
authors: Mueck
authors: Dagmar
authors: D
authors: Kubitza
authors: Richard J
authors: RJ
authors: Bauer
authors: Hong
authors: H
authors: Zhang
authors: Yimin
authors: Y
authors: Cui
mesh_terms: D000293:Adolescent; D000328:Adult; D000990:Antithrombin III / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D044466:Asian People / Q000208:ethnology; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000069552:Rivaroxaban; D016037:Single-Blind Method; D013876:Thiophenes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D055815:Young Adult
chemical_list: D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000990:Antithrombin III; D000069552:Rivaroxaban