别嘌醇和氯贝丁酯对人体中香豆素类抗凝剂消除的影响。
The effects of allopurinol and clofibrate on the elimination of coumarin anticoagulants in man.
作者信息
Pond S M, Graham G G, Wade D N, Sudlow G
出版信息
Aust N Z J Med. 1975 Aug;5(4):324-8. doi: 10.1111/j.1445-5994.1975.tb03266.x.
The effects of chronic treatment with allopurinol and clofibrate on the elimination from plasma of warfarin and dicoumarol were examined in man. In addition, the binding of warfarin to human serum proteins was measured with and without clofibrate and its metabolite chlorophenoxyisobutyric acid (CPIB), both present in therapeutic concentrations. Treatment with allopurinol and clofibrate did not alter the rate of elimination of warfarin from plasma. In addition, clofibrate and CPIB caused no significant displacement of warfarin from serum proteins. This evidence supports the conclusion that the clinically significant potentiation of warfarin activity by clofibrate in man is due to an interaction at the receptor site. In contrast, treatment with allopurinol resulted in significant prolongation of the plasma half-life of dicoumarol in one of three subjects. These data are consistent with inhibition of the metabolism of dicoumarol by allopurinol in some individuals.
在人体中研究了别嘌醇和氯贝丁酯长期治疗对华法林和双香豆素从血浆中消除的影响。此外，测定了在有和没有治疗浓度的氯贝丁酯及其代谢产物氯苯氧异丁酸（CPIB）存在的情况下华法林与人血清蛋白的结合情况。别嘌醇和氯贝丁酯治疗并未改变华法林从血浆中的消除速率。此外，氯贝丁酯和CPIB未引起华法林从血清蛋白上的显著置换。这一证据支持了氯贝丁酯在人体中对华法林活性产生临床显著增强作用是由于在受体部位发生相互作用这一结论。相比之下，在三名受试者中的一名中，别嘌醇治疗导致双香豆素的血浆半衰期显著延长。这些数据与别嘌醇在某些个体中抑制双香豆素代谢一致。
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