华法林稳态时的药代动力学和药效学
Pharmacokinetics and pharmacodynamics of warfarin at steady state.
作者信息
Routledge P A, Chapman P H, Davies D M, Rawlins M D
出版信息
Br J Clin Pharmacol. 1979 Sep;8(3):243-7. doi: 10.1111/j.1365-2125.1979.tb01009.x.
Abstract
1 The relationship between warfarin dose, total and free plasma warfarin concentration, and anticoagulant effect was examined at several steady-state levels in fifteen patients during withdrawal of warfarin therapy. 2 Total plasma clearance was significantly correlated with the free fraction in plasma (r=0.955). 3 There was an age related decline in the dose of warfarin, and in the total and free plasma warfarin concentrations required to produce the same anticoagulant effect. However, neither total nor free plasma warfarin clearances varied with age. 4 Individual patients' log concentration-effect relationships were linear above a prothrombin ratio of 1.2 and there was a significant correlation (r=-0.586) between the slope and the free fraction of warfarin in plasma. It is suggested that plasma protein binding may reflect the interaction between warfarin and its effector site in the hepatocyte.
摘要
- 在15例患者停用华法林治疗期间的几个稳态水平下，研究了华法林剂量、血浆总华法林浓度和游离华法林浓度与抗凝效果之间的关系。2. 血浆总清除率与血浆中游离分数显著相关（r = 0.955）。3. 华法林剂量以及产生相同抗凝效果所需的血浆总华法林浓度和游离华法林浓度存在与年龄相关的下降。然而，血浆总华法林清除率和游离华法林清除率均不随年龄变化。4. 个体患者的对数浓度 - 效应关系在凝血酶原比值高于1.2时呈线性，并且斜率与血浆中华法林的游离分数之间存在显著相关性（r = -0.586）。提示血浆蛋白结合可能反映了华法林与其在肝细胞效应位点之间的相互作用。
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