Kubitza D, Becka M, Roth A, Mueck W
Clinical Pharmacology, Bayer Pharma AG, Wuppertal, Germany.
J Int Med Res. 2012;40(5):1688-707. doi: 10.1177/030006051204000508.
To investigate potential interactions between rivaroxaban, an oral direct Factor Xa inhibitor approved for the management of thromboembolic disorders, and digoxin or atorvastatin.
Two randomized, phase 1 clinical trials were undertaken in healthy men to assess pharmacokinetic and pharmacodynamic interactions between rivaroxaban and digoxin or atorvastatin, and the safety of these drug combinations.
Steady-state rivaroxaban did not affect the pharmacokinetic profile of steady-state digoxin (n = 17). Digoxin did not significantly influence the pharmacokinetic profile of single-dose rivaroxaban and had minimal effects on rivaroxaban-induced inhibition of Factor Xa activity and prolongation of clotting time. Similarly, steady-state atorvastatin did not affect the pharmacokinetic profile or the pharmacodynamics of rivaroxaban and vice versa (n = 19). All drugs (alone or in combination) were well tolerated.
There were no clinically relevant pharmacokinetic or pharmacodynamic interactions between rivaroxaban and digoxin, or between rivaroxaban and atorvastatin, suggesting that rivaroxaban can be coadministered with either drug. This study also confirmed that rivaroxaban does not interact with substrates for permeability (P)-glycoprotein alone (digoxin) or P-glycoprotein and cytochrome P(450) (CYP)3A4 (atorvastatin).
研究已被批准用于治疗血栓栓塞性疾病的口服直接Xa因子抑制剂利伐沙班与地高辛或阿托伐他汀之间的潜在相互作用。
在健康男性中进行了两项1期随机临床试验，以评估利伐沙班与地高辛或阿托伐他汀之间的药代动力学和药效学相互作用，以及这些药物组合的安全性。
稳态利伐沙班不影响稳态地高辛的药代动力学特征（n = 17）。地高辛对单剂量利伐沙班的药代动力学特征无显著影响，对利伐沙班诱导的Xa因子活性抑制和凝血时间延长的影响极小。同样，稳态阿托伐他汀不影响利伐沙班的药代动力学特征或药效学，反之亦然（n = 19）。所有药物（单独或联合使用）耐受性良好。
利伐沙班与地高辛之间或利伐沙班与阿托伐他汀之间不存在临床相关的药代动力学或药效学相互作用，这表明利伐沙班可与这两种药物联合使用。本研究还证实，利伐沙班不与单独的通透性（P）-糖蛋白底物（地高辛）或P-糖蛋白和细胞色素P（450）（CYP）3A4底物（阿托伐他汀）相互作用。
