Kelly J G, O'Malley K
Clin Pharmacokinet. 1979 Jan-Feb;4(1):1-15. doi: 10.2165/00003088-197904010-00001.
Warfarin is clinically the most widely used oral anticoagulant and its properties have been extensively studied. Assay method for these compounds have until recently been relatively nonspecific. The advent of chromatographically based techniques has enabled re-evaluation of the pharmacokinetics of oral anticoagulants, but most work continues to involve warfarin. The most important recent work has concerned the different anticoagulant potencies and metabolic pathways of the optical isomers of some of these drugs. The effects of age and some diseases on pharmacokinetics of warfarin have been examined but much remains to be done, especially with oral anticoagulants other than warfarin. There are several well established pharmacokinetic drug interactions with warfarin. There is a wide awareness of the drugs most likely to reduce anticoagulant effects by enzyme induction and alternative drugs can be used. Mechanisms of some interactions have been re-investigated. In vivo drug displacement interactions are complicated by the correlation between hepatic clearance of these drugs and the size of the unbound fraction in plasma. The interactions between phenylbutazone and warfarin and metronidazole and warfarin, resulting in potentiation of anticoagulant effect have been suggested to be due mainly to an inhibition of the metabolism of the more potent S isomer of warfarin.
华法林是临床上使用最广泛的口服抗凝剂，其特性已得到广泛研究。直到最近，这些化合物的测定方法相对缺乏特异性。基于色谱技术的出现使得重新评估口服抗凝剂的药代动力学成为可能，但大多数研究仍围绕华法林展开。近期最重要的研究涉及其中一些药物光学异构体的不同抗凝效力和代谢途径。年龄和某些疾病对华法林药代动力学的影响已得到研究，但仍有许多工作有待开展，尤其是针对华法林以外的口服抗凝剂。华法林存在几种已明确的药代动力学药物相互作用。人们普遍知晓最有可能通过酶诱导降低抗凝效果的药物，并且可以使用替代药物。一些相互作用的机制已重新进行研究。体内药物置换相互作用因这些药物的肝清除率与血浆中游离部分大小之间的相关性而变得复杂。已表明保泰松与华法林以及甲硝唑与华法林之间的相互作用会增强抗凝效果，这主要归因于对更具活性的华法林S异构体代谢的抑制。
