West Virginia Center for Drug and Health Information, Morgantown, 26506, USA.
Am J Health Syst Pharm. 2011 Aug 15;68(16):1506-19. doi: 10.2146/ajhp100348.
The pharmacology, pharmacokinetics, clinical efficacy, tolerability, dosage and administration, and place in therapy of dabigatran etexilate are reviewed.
Dabigatran is a reversible direct thrombin inhibitor (DTI) that has rapid and predictable anticoagulant effects and does not require the anticoagulation monitoring seen with oral vitamin K antagonists. Dabigatran etexilate has demonstrated efficacy in several clinical studies in preventing venous thromboembolism (VTE) for patients undergoing total hip or knee replacement, in preventing strokes in patients with nonvalvular atrial fibrillation, and in treating acute VTE. Dabigatran etexilate is a prodrug that is orally absorbed and completely converted to the active form dabigatran by carboxylesterases. Neither the conversion of dabigatran etexilate nor the metabolism of active dabigatran involves the cytochrome P-450 isoenzyme system. Other than hemorrhage, dabigatran is generally well tolerated, with gastrointestinal effects being the most commonly reported adverse events. All dosages should be adjusted in patients with reduced renal function. Dabigatran is currently being investigated for several thromboembolic disorders. It was approved by the Food and Drug Administration in October 2010 for stroke and VTE prevention in adult patients with nonvalvular atrial fibrillation, and it was approved by the European Medicines Agency in March 2009 for the prevention of VTE in adult patients undergoing elective total hip or knee replacement.
Dabigatran etexilate, the first oral DTI marketed in the United States, is indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Dabigatran may be a viable option for anticoagulation in some patients due to its oral administration, rapid onset of action, and predictable anticoagulant effects.
本文回顾了达比加群酯的药理学、药代动力学、临床疗效、耐受性、剂量和给药方法以及在治疗中的地位。
达比加群酯是一种可逆的直接凝血酶抑制剂（DTI），具有快速且可预测的抗凝作用，无需像口服维生素 K 拮抗剂那样进行抗凝监测。达比加群酯已在多项临床研究中证明了其在预防全髋关节或膝关节置换术后静脉血栓栓塞症（VTE）、预防非瓣膜性心房颤动患者中风以及治疗急性 VTE 方面的疗效。达比加群酯是一种前体药物，口服吸收后完全由羧酸酯酶转化为活性形式达比加群。达比加群酯的转化和活性达比加群的代谢均不涉及细胞色素 P-450 同工酶系统。除出血外，达比加群一般耐受性良好，胃肠道反应是最常见的不良反应。所有剂量均应根据肾功能降低的患者进行调整。达比加群目前正在研究几种血栓栓塞性疾病。它于 2010 年 10 月获得美国食品和药物管理局批准，用于预防非瓣膜性心房颤动成年患者的中风和 VTE，于 2009 年 3 月获得欧洲药品管理局批准，用于预防接受择期全髋关节或膝关节置换术的成年患者的 VTE。
达比加群酯是美国市场上第一种上市的口服 DTI，用于降低非瓣膜性心房颤动患者中风和全身性栓塞的风险。由于达比加群酯可口服、起效迅速且具有可预测的抗凝作用，因此可能成为某些患者抗凝治疗的一种可行选择。
