新的口服抗凝血剂:比较药理学和维生素K拮抗剂。

文章的细节

引用
复制到剪贴板

Scaglione F

新的口服抗凝血剂:比较药理学和维生素K拮抗剂。

Pharmacokinet。2013年2月,52 (2):69 - 82。doi: 10.1007 / s40262 - 012 - 0030 - 9。

PubMed ID
23292752 (在PubMed
]
文摘

新的口服抗凝血剂(OACs)直接抑制因子Xa(——)或凝血酶开发的长期预防血栓栓塞疾病。这些小说代理提供很多好处在年长的维生素K拮抗剂(VKAs)由于主要药理差异。VKAs经济特征很好,但有重要的限制,这些限制会超过这些优势,如出现行动缓慢,治疗窗窄,不可预知的抗凝效果。VKA-associated饮食预防、监测和剂量调整维护国际标准化比率(INR)在治疗范围内,和桥接治疗,是患者不方便,昂贵的,可能会导致不适当的使用VKA治疗。这可能导致出血风险增加或减少抗凝和血栓事件的风险增加。新OACs迅速开始行动,为食品和药物相互作用低电位,可预测的抗凝效果,消除了常规监测的必要性。FXa抑制剂,如rivaroxaban和apixaban有力,口服prothrombinase-bound的直接抑制剂,clot-associated——或免费。代理都迅速开始行动,广泛的治疗窗,很少或没有与食品和其他药物,最小inter-patient可变性,并显示类似的药物动力学在不同的患者群体。因为基质,合并施打rivaroxaban和apixaban强大的细胞色素P450 (CYP) 3 a4和渗透率糖蛋白(P-gp)抑制剂和诱导物会导致大量的血浆浓度的变化将改变间隙率;因此,同时使用禁忌和谨慎使用时需要与强大的CYP3A4和P-gp抗病诱导剂。 Although parenteral oral direct thrombin inhibitors (DTIs), such as argatroban and bivalirudin, have been on the market for years, DTIs such as dabigatran are novel synthetic thrombin antagonists. Dabigatran etexilate is a low-molecular-weight non-active pro-drug that is administered orally and converted rapidly to its active form, dabigatran--a potent, competitive and reversible DTI. Dabigatran has an advantage over the indirect thrombin inhibitors, unfractionated heparin and low-molecular-weight heparin, in that it inhibits free and fibrin-bound thrombin. The reversible binding of dabigatran may provide safer and more predictable anticoagulant treatment than seen with irreversible, non-covalent thrombin inhibitors, e.g. hirudin. Dabigatran shows a very low potential for drug-drug interactions. However, co-administration of dabigatran etexilate with other anticoagulants and antiplatelet agents can increase the bleeding risk. Although the new agents are pharmacologically better than VKAs--particularly in terms of fixed dosing, rapid onset of action, no INR monitoring and lower risk of drug interactions--there are some differences between them: the bioavailability of dabigatran is lower than rivaroxaban and apixaban, and so the dabigatran dosage required is higher; lower protein binding of dabigatran reduces the variability related to albuminaemia. The risk of metabolic drug-drug interactions also appears to differ between OACs: VKAs > rivaroxaban > apixaban > dabigatran. The convenience of the new OACs has translated into improvements in efficacy and safety as shown in phase III randomized trials. The new anticoagulants so far offer the greatest promise and opportunity for the replacement of VKAs.

DrugBank数据引用了这篇文章

药物
药物转运蛋白
药物 转运体 类 生物 药理作用 行动
Dabigatran etexilate 22 - 1 蛋白质 人类
未知的
底物
 细节