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标题：EFFECT OF FUROSEMIDE ON PLASMA CLEARANCE, ANTICOAGU-LANT EFFECT AND PROTEIN BINDING OF WARFARIN IN RATS
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作者：TARO OGISO ; MASAHIRO IWAKI ; YOSHIMASA KONISHI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1982
卷号：5
期号：10
页码：829-840
DOI：10.1248/bpb1978.5.829
出版社：The Pharmaceutical Society of Japan
摘要：The effect of furosemide on the elimination, anticoagulant effect and the in vitro and in vivo protein bindings of warfarin was examined in rats. The pharmacokinetic parameters of warfarin and prothrombin complex activity (PCA) after a single i.v. coadministration with warfarin (1.2 mg/kg) and furosemide (1.67 mg/kg) were not significantly different as compared with those in the group injected warfarin alone; however when coadministered with 5 mg/kg of furosemide, the elimination rate constant was significantly increased and PCA was markedly enhanced beyond 60 h after administration. The concurrent treatment with warfarin and a higher dose (10 mg/kg) of furosemide caused an increase in the anticoagulant effect of warfarin even at earier periods after administration. Both the unbound warfarin concentration in serum at 30 min and the amount of warfarin extracted into liver at 2 h after a single i.v. dosing in the coadministered group were significantly increased as compared with those in the group received warfarin alone. Results from in vitro binding studies using bovine serum albumin and rat plasma showed a typical competitive nature of protein binding of warfarin and furosemide at the same binding sites. These results suggest that the interactions, such as the displacement of warfarin binding at albumin binding sites, between warfarin and furosemide are produced, when a high dose of furosemide was coadministered.
关键词：displacement of warfarin from protein binding sites