Safety, pharmacokinetics and pharmacodynamics of single doses of rivaroxaban - an oral, direct factor Xa inhibitor - in elderly Chinese subjects
Safety, pharmacokinetics and pharmacodynamics of single doses of rivaroxaban - an oral, direct factor Xa inhibitor - in elderly Chinese subjects
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DOI：
10.1160/th09-03-0196
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发表时间：
2010-01-01
影响因子：
6.7
通讯作者：
Hu, Pei
中科院分区：
文献类型：
--
作者：
Jiang, Ji;Hu, Yufang;Hu, Pei
利伐沙班是一种新型的口服直接因子Xa(FXA)抑制剂，用于预防和治疗血栓栓塞性疾病。本研究的目的是考察利伐沙班在健康老年受试者中的安全性、药动学和药效学。在这项单中心、单盲、安慰剂对照、平行分组的剂量递增研究中，79名年龄在59-74岁(平均62.8岁)的受试者被随机分为5、10、20、30或40毫克每天口服一次利伐沙班。利伐沙班耐受性良好：紧急治疗的不良事件发生率很低，所有事件的强度都很小。利伐沙班吸收迅速，在2-4小时内达到最大血药浓度。利伐沙班的PK在所测试的剂量范围内呈剂量依赖性。FXA的最大抑制出现在给药后2-3小时，24-48小时后恢复到基线水平，反映了利伐沙班的血药浓度。对FXA的抑制与全球凝血试验的剂量依赖效应有关。在男性和女性受试者之间，利伐沙班的血药浓度在临床上没有相关差异。总之，利伐沙班耐受性良好，在健康的老年中国受试者中发现有可预测的PK和PD。
Rivaroxaban is a novel, oral, direct factor Xa (FXa) inhibitor for the prevention and treatment of thromboembolic disorders. The aim of this study was to investigate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in healthy, elderly Chinese subjects. In this single-centre, single-blind, placebo-controlled, parallel-group, dose-escalation study, 79 subjects, aged 59-74 years (mean 62.8), were randomised to receive once-daily oral doses of rivaroxaban 5,10, 20, 30 or 40 mg. Rivaroxaban was well tolerated: there was a low incidence of treatment-emergent adverse events and all events were of mild intensity. Rivaroxaban was absorbed rapidly, reaching maximum plasma concentrations within 2-4 hours. The PK of rivaroxaban were dose dependent over the dose range tested. Maximal inhibition of FXa occurred 2-3 hours after dosing and returned to baseline after 24-48 hours, reflecting rivaroxaban plasma concentrations. Inhibition of FXa was associated with dose-dependent effects on global clotting tests. There were no clinically relevant differences in rivaroxaban plasma concentrations between male and female subjects. In conclusion, rivaroxaban was well tolerated and was found to have predictable PK and PD in healthy, elderly Chinese subjects.