Serum protein binding as a determinant of warfarin body clearance and anticoagulant effect
Serum protein binding as a determinant of warfarin body clearance and anticoagulant effect
复制标题
血清蛋白结合是华法林体内清除和抗凝作用的决定因素
DOI：
10.1002/cpt1976195part1552
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发表时间：
1976
影响因子：
6.7
通讯作者：
G. Levy
中科院分区：
文献类型：
--
作者：
Avraham Vacobi;J. Udall;G. Levy
在 31 名定期服用华法林的心血管疾病患者中测定了华法林的血清蛋白结合和消除动力学。血清中华法林的游离分数范围为0.00436至0.0189，表明蛋白结合率为98.11%至99.56%。华法林的蛋白结合程度与血清中白蛋白或总蛋白的浓度之间没有明显的关系。患者体内华法林的估计总体清除率范围为 1.16 至 4.35 ml/hr/kg 体重，与血清中华法林的游离分数显着相关。这种相关性已在理论基础上得到预测，并表明血清蛋白结合是华法林在人体中消除动力学的主要决定因素，也是其体内清除率个体间差异的重要原因。凝血酶原时间相似的患者血清中游离华法林浓度的个体间差异略小于血清华法林总浓度和华法林每日剂量的差异。凝血酶原时间与血清中游离华法林浓度之间没有相关性，表明除蛋白结合之外的变量也影响患者的抗凝反应。
The serum protein binding and elimination kinetics of warfarin were determined in 31 patients with cardiovascular disease who were taking warfarin regularly. The free fraction of warfarin in the serum ranged from 0.00436 to 0.0189, indicating 98.11% to 99.56% protein binding. There was no apparent relationship between the extent of protein binding of warfarin and the concentration of albumin or total protein in the serum. The estimated total body clearance of warfarin in the patients ranged from 1.16 to 4.35 ml/hr/kg of body weight and correlated significantly with the free fraction of warfarin in serum. This correlation has been predicted on theoretical grounds and shows that serum protein binding is a major determinant of the elimination kinetics of warfarin in man and an important cause of interindividual variations in its body clearance. The inter individual variation of free warfarin concentrations in the serum of patients with similar prothrombin times was somewhat smaller than the variations in total serum‐warfarin concentrations and in the daily dose of warfarin. There was no correlation between prothrombin time and the concentration of free warfarin in serum, indicating that variables other than protein binding also affect the anticoagulant response of patients.