Loyola University Medical Center, Maywood, IL 60153, USA.
J Clin Pharmacol. 2010 Sep;50(9):986-1000. doi: 10.1177/0091270009355814. Epub 2010 Feb 2.
Interpatient variability in the safety and efficacy of oral anticoagulation with warfarin presents several challenges to clinicians, thus underscoring the emergent need for new orally available anticoagulants with predictable pharmacokinetic and pharmacodynamic profiles and ability to target circulating clotting factors. Seven compounds including rivaroxaban, apixaban, betrixaban, and eribaxaban are orally available direct inhibitors of activated factor X currently in development for the prevention and treatment of venous thromboembolism and for thromboprophylaxis in patients with atrial fibrillation or following an acute coronary syndrome. At doses used in phase 2 and 3 clinical trials, rivaroxaban and apixaban demonstrated a predictable onset of effect, maximal plasma concentration, and half-life that was unaffected by age, renal, or hepatic disease. In clinical trials for the treatment and prevention of venous thromboembolism, rivaroxaban and apixaban produced equivalent or superior reductions in the development or progression of venous thromboembolism compared with either low molecular weight heparin or warfarin. Trials comparing the efficacy of rivaroxaban or apixaban to standard therapy for stroke prophylaxis in patients with atrial fibrillation are in process. Rivaroxaban, the sentinel compound in this class, is already approved in the European Union and Canada. It is likely to be approved for use in the United States in 2010.
华法林口服抗凝治疗的患者间安全性和疗效的变异性给临床医生带来了诸多挑战，这突显了开发新的、可预测药代动力学和药效学特征的、能够靶向循环凝血因子的口服可用抗凝剂的迫切需要。目前正在开发的 7 种化合物，包括利伐沙班、阿哌沙班、贝曲沙班和依度沙班，是口服有效的、已激活的因子 X 直接抑制剂，用于预防和治疗静脉血栓栓塞症，以及预防房颤或急性冠脉综合征患者的血栓形成。在 2 期和 3 期临床试验中使用的剂量下，利伐沙班和阿哌沙班的作用起效、最大血浆浓度和半衰期具有可预测性，不受年龄、肾功能或肝功能的影响。在治疗和预防静脉血栓栓塞症的临床试验中，与低分子肝素或华法林相比，利伐沙班和阿哌沙班在静脉血栓栓塞症的发展或进展方面产生了等效或更优的降低效果。比较利伐沙班或阿哌沙班与房颤患者卒中预防标准治疗的疗效的试验正在进行中。利伐沙班是该类药物中的先导化合物，已在欧盟和加拿大获得批准。它很可能在 2010 年在美国获得批准使用。
