Thomas Jefferson University Hospital, Department of Pharmacy - Vascular Medicine , 111 South 10th St, Philadelphia, PA 19107 , USA +1609 706 5271 ;
Expert Opin Investig Drugs. 2013 Nov;22(11):1465-72. doi: 10.1517/13543784.2013.825605. Epub 2013 Aug 22.
For over 60 years vitamin K antagonists have been the mainstay of oral therapy for treatment and prevention of venous and arterial thromboembolic disease. The emergence of two new classes of orally administered anticoagulants, direct thrombin and factor Xa inhibitors have drastically changed the landscape in the management of these disease states. Betrixaban , an orally administered direct factor Xa inhibitor, is entering a Phase III trial and undergoing investigation for similar indications as apixaban, dabigatran and rivaroxaban.
The chemical development of betrixaban, pharmacokinetic differences between betrixaban and currently available novel anticoagulants and future considerations for clinical use.
Betrixaban, the fifth novel oral anticoagulant in line for the Food and Drug Administration (FDA) approval, possesses some unique pharmacokinetic characteristics in comparison with the currently available novel anticoagulants, including limited renal excretion, minimal metabolism through the cytochrome p450 system and a long half-life. This pharmacokinetic profile may allow greater flexibility for use in patients with poor renal function, offer the convenience of once daily dosing, and exhibit less drug interactions. Betrixaban is currently being evaluated for prophylaxis against venous thromboembolic disease (VTED) and the prevention of stroke and systemic embolism associated with nonvalvular atrial fibrillation, its role in the management of acute VTED and acute coronary syndromes is yet to be defined based on clinical data and evaluation. Of interest, a factor Xa decoy, PRT4445, is currently under evaluation in conjunction with betrixaban, and may be a universal reversal agent for all anticoagulants with anti-Xa activity. Currently, there are no specific reversal agents for the novel anticoagulants. The availability of an effective reversal agent would be very attractive for the management of associated bleeding, bleeding due to trauma, or the need for emergent surgery.
60 多年来，维生素 K 拮抗剂一直是治疗和预防静脉和动脉血栓栓塞性疾病的口服治疗的主要药物。两类新型口服抗凝剂，即直接凝血酶和因子 Xa 抑制剂的出现，极大地改变了这些疾病状态的治疗格局。贝曲西班，一种口服直接因子 Xa 抑制剂，正在进行 III 期临床试验，并正在研究与阿哌沙班、达比加群和利伐沙班类似的适应症。
贝曲西班的化学开发、贝曲西班与目前可用的新型抗凝剂之间的药代动力学差异以及未来临床应用的考虑因素。
贝曲西班是第五种获得美国食品和药物管理局（FDA）批准的新型口服抗凝剂，与目前可用的新型抗凝剂相比，具有一些独特的药代动力学特征，包括有限的肾脏排泄、通过细胞色素 P450 系统的最小代谢和较长的半衰期。这种药代动力学特征可能使贝曲西班在肾功能不佳的患者中使用更加灵活，提供每日一次给药的便利，并表现出较少的药物相互作用。贝曲西班目前正在评估其用于预防静脉血栓栓塞性疾病（VTED）和预防非瓣膜性心房颤动相关的中风和系统性栓塞的用途，其在急性 VTED 和急性冠状动脉综合征的管理中的作用尚未根据临床数据和评估来确定。有趣的是，一种因子 Xa 诱饵 PRT4445 目前正在与贝曲西班一起评估，并且可能是所有具有抗 Xa 活性的抗凝剂的通用逆转剂。目前，新型抗凝剂没有特定的逆转剂。有效的逆转剂的可用性对于管理相关出血、创伤引起的出血或紧急手术的需要将非常有吸引力。
