Safety, pharmacokinetics and pharmacodynamics of single/multiple doses of the oral, direct Factor Xa inhibitor rivaroxaban in healthy Chinese subjects.
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.
Zhao
Xia
X
Medical Department, Bayer HealthCare Company Ltd., Beijing, China.
Sun
Peihong
P
Zhou
Ying
Y
Liu
Yuwang
Y
Zhang
Huilin
H
Mueck
Wolfgang
W
Kubitza
Dagmar
D
Bauer
Richard J
RJ
Zhang
Hong
H
Cui
Yimin
Y
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
D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000990:Antithrombin III; D000069552:Rivaroxaban