|Safety, pharmacokinetics and pharmacodynamics of single/multiple doses of the oral, direct Factor Xa inhibitor rivaroxaban in healthy Chinese subjects|
|Zhao, Xia1; Sun, Peihong1; Zhou, Ying1; Liu, Yuwang1; Zhang, Huilin1; Mueck, Wolfgang3; Kubitza, Dagmar3; Bauer, Richard J.4; Zhang, Hong2; Cui, Yimin1|
|关键词||Anticoagulant Chinese Subjects Factor Xa Inhibitor Rivaroxaban|
|刊名||BRITISH JOURNAL OF CLINICAL PHARMACOLOGY|
|WOS标题词||Science & Technology|
|类目[WOS]||Pharmacology & Pharmacy|
|研究领域[WOS]||Pharmacology & Pharmacy|
|关键词[WOS]||TOTAL HIP-REPLACEMENT ; DEEP-VEIN THROMBOSIS ; VENOUS THROMBOEMBOLISM ; BAY 59-7939 ; ATRIAL-FIBRILLATION ; BAY-59-7939 ; PREVENTION ; ANTICOAGULATION ; PREVALENCE ; ISSUES|
center dot Rivaroxaban is an oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders.
center dot In single- and multiple-dose Phase I studies in White subjects, rivaroxaban was safe and demonstrated predictable, dose-dependent pharmacokinetics and pharmacodynamics.
WHAT THIS STUDY ADDS
center dot The Phase III programme with rivaroxaban is being conducted worldwide.
center dot Therefore, it is necessary to determine whether the pharmacokinetics, pharmacodynamics and tolerability of rivaroxaban are altered in patients of different ethnic origins.
center dot Dose-escalation studies were conducted to determine the safety, pharmacokinetics and pharmacodynamics of single and multiple doses of rivaroxaban in healthy Chinese subjects.
To investigate the safety, pharmacokinetics and pharmacodynamics of rivaroxaban, an oral, direct Factor Xa (FXa) inhibitor, in healthy, male Chinese subjects.
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.
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.
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.
|资助机构||Bayer Schering Pharma AG|
|作者单位||1.Bayer Schering Pharma AG, Clin Pharmacol, Wuppertal, Germany|
2.Peking Univ, Hosp 1, Dept Pharm, Beijing 100034, Peoples R China
3.Bayer HealthCare Co Ltd, Dept Med, Beijing, Peoples R China
4.Bayer Schering Pharma AG, Med Affairs Asia Pacific, Wuppertal, Germany
|Zhao, Xia,Sun, Peihong,Zhou, Ying,et al. Safety, pharmacokinetics and pharmacodynamics of single/multiple doses of the oral, direct Factor Xa inhibitor rivaroxaban in healthy Chinese subjects[J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY,2009,68(1):77-88.|
|APA||Zhao, Xia.,Sun, Peihong.,Zhou, Ying.,Liu, Yuwang.,Zhang, Huilin.,...&Cui, Yimin.(2009).Safety, pharmacokinetics and pharmacodynamics of single/multiple doses of the oral, direct Factor Xa inhibitor rivaroxaban in healthy Chinese subjects.BRITISH JOURNAL OF CLINICAL PHARMACOLOGY,68(1),77-88.|
|MLA||Zhao, Xia,et al."Safety, pharmacokinetics and pharmacodynamics of single/multiple doses of the oral, direct Factor Xa inhibitor rivaroxaban in healthy Chinese subjects".BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 68.1(2009):77-88.|