比较药物动力学的维生素K拮抗剂:华法林,phenprocoumon和苊香豆醇。
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佛罗里达大学M
比较药物动力学的维生素K拮抗剂:华法林,phenprocoumon和苊香豆醇。
Pharmacokinet。2005; 44 (12): 1227 - 46。
- PubMed ID
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16372822 (在PubMed]
- 文摘
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维生素K拮抗剂属于全球最常用药物的集团。他们是用于长期抗凝治疗,展示他们的抗凝效果环氧维生素K还原酶的抑制作用。每种药物存在于两个不同的对映体形式和口服药物为外消旋体。维生素K拮抗剂的使用是复杂的狭窄的治疗指数和不可预知的剂量反应关系,导致频繁出血并发症或抗凝不足。这些大剂量反应差异显著影响药代动力学方面,是由遗传决定的,环境和其他未知因素。以前在这方面的知识主要是指华法林。细胞色素P450 (CYP) 2 c9显然已经被建立为主要负责新陈代谢的催化剂s对映体更有效。最近,CYP2C9也被报道的羟基化催化phenprocoumon和苊香豆醇。然而,CYP2C9的相对重要性每个抗凝的间隙明显不同。总的来说,CYP2C9同工酶对华法林的间隙似乎是最重要的,其次是苊香豆醇,最后,phenprocoumon。 The less important role of CYP2C9 for the clearance of phenprocoumon is due to the involvement of CYP3A4 as an additional catalyst of phenprocoumon hydroxylation and significant excretion of unchanged drug in bile and urine, while the elimination of warfarin and acenocoumarol is almost completely by metabolism. Consequently, the effects of CYP2C9 polymorphisms on the pharmacokinetics and anticoagulant response are also least pronounced in the case of phenprocoumon; this drug seems preferable for therapeutic anticoagulation in poor metabolisers of CYP2C9. In addition to these vitamin K antagonists, oral thrombin inhibitors are currently under clinical development for the prevention and treatment of thromboembolism. Of these, ximelagatran has recently gained marketing authorisation in Europe. These novel drugs all feature some major advantages over traditional anticoagulants, including a wide therapeutic interval, the lack of anticoagulant effect monitoring and a low drug-drug interaction potential. However, they are also characterised by some pitfalls. Amendments of traditional anticoagulant therapy, including self-monitoring of international normalised ratio values or prospective genotyping for individual dose-tailoring may contribute to the continuous use of warfarin, phenprocoumon and acenocoumarol in the future.
DrugBank数据引用了这篇文章
- 药物
- 药物酶
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药物 酶 类 生物 药理作用 行动 苊香豆醇 细胞色素P450 3 a4 蛋白质 人类 未知的底物细节 华法令阻凝剂 细胞色素P450 1 a2 蛋白质 人类 未知的底物细节 华法令阻凝剂 细胞色素P450 2 c18 蛋白质 人类 未知的底物细节 华法令阻凝剂 细胞色素P450 2 c19 蛋白质 人类 未知的底物抑制剂细节 华法令阻凝剂 细胞色素P450 2 c8 蛋白质 人类 未知的底物细节 华法令阻凝剂 细胞色素P450 2 c9 蛋白质 人类 未知的底物诱导物细节 华法令阻凝剂 细胞色素P450 3 a4 蛋白质 人类 未知的底物诱导物细节 Ximelagatran 细胞色素P450 2 c9 蛋白质 人类 未知的底物细节 - 药物反应
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反应 细节 细节 细节 细节 细节 细节 细节 细节 细节
