Chan Noel C, Hirsh Jack, Ginsberg Jeffrey S, Eikelboom John W
Thrombosis & Atherosclerosis Research Institute, C3-10 DBCVRSI, Hamilton General Hospital, 237 Barton Street East, Hamilton, ON L8L 2X2, Canada.
Future Cardiol. 2014 Jan;10(1):43-52. doi: 10.2217/fca.13.98.
The recently introduced oral anticoagulants, dabigatran, rivaroxaban and apixaban, were shown, in randomized controlled trials, to be at least as effective and safe as monitored warfarin therapy for the treatment of venous thromboembolism and stroke prevention in atrial fibrillation. These new oral anticoagulants have predictable pharmacology, less variability in anticoagulant effect and fewer drug and food interactions than warfarin, allowing unmonitored and fixed dosing, which renders their use appealing. The remaining limitations of currently available new oral anticoagulants include their dependence on renal and hepatic clearance, and the lack of an antidote, which is problematic in bleeding patients and those requiring urgent surgery. Betrixaban is a new direct factor Xa inhibitor with distinct pharmacological characteristics, including a long half-life, minimal renal clearance and minimal hepatic metabolism. Betrixaban was tested in Phase II studies in orthopedic thromboprophylaxis (EXPERT) and atrial fibrillation (EXPLORE-Xa), and is being evaluated in a Phase III trial of extended thromboprophylaxis in medical patients (APEX). This article details the pharmacology, preclinical and clinical development of betrixaban.
近期上市的口服抗凝剂达比加群、利伐沙班和阿哌沙班在随机对照试验中表明，在治疗静脉血栓栓塞和预防房颤中风方面，其疗效和安全性至少与监测华法林治疗相当。这些新型口服抗凝剂具有可预测的药理学特性，与华法林相比，抗凝效果的变异性更小，药物与食物相互作用更少，无需监测且剂量固定，因此其应用颇具吸引力。目前可用的新型口服抗凝剂尚存的局限性包括依赖肾和肝清除，且缺乏解毒剂，这在出血患者和需要紧急手术的患者中存在问题。贝曲西班是一种新型直接Xa因子抑制剂，具有独特的药理学特性，包括半衰期长、肾清除率极低和肝代谢极少。贝曲西班已在骨科血栓预防（EXPERT）和房颤（EXPLORE-Xa）的II期研究中进行了测试，目前正在一项针对内科患者延长血栓预防的III期试验（APEX）中进行评估。本文详细介绍了贝曲西班的药理学、临床前和临床开发情况。
