Bjornsson T D, Meffin P J, Swezey S E, Blaschke T F
J Pharmacol Exp Ther. 1979 Sep;210(3):322-6.
Clofibrate may interact with warfarin by potentiating its effects on vitamin K disposition. To examine this possibility, specifically labeled [3H]vitamin K was given intravenously to four healthy volunteers under conditions of no drug administration, administration of warfarin or clofibrate alone, or co-administration of both drugs. Clofibrate alone did not affect the disposition of tritiated vitamin K. Warfarin alone produced an accumulation in plasma of substantial amounts of vitamin K epoxide, a metabolite of vitamin K which is reconverted to vitamin K by a specific reductase. Although reconversion is apparently blocked to a large extent by warfarin, the plasma disappearance of tritiated vitamin K in the presence of warfarin is almost superimpossible to that observed in the absence of drugs. Clofibrate coadministration did not result in greater accumulation of vitamin K epoxide in plasma. These results indicate that clofibrate does not enhance the inhibition of the reductase enzyme. Analysis of the tritiated vitamin K plasma disappearance data indicates that the pool size of vitamin K in the body is small, and is turned over almost 10 times daily. The vitamin K epoxide data suggest that, in the absence of drugs, a relatively small proportion of the epoxide is reconverted to the vitamin.
氯贝丁酯可能通过增强华法林对维生素K代谢的影响而与之相互作用。为了检验这种可能性，在未给药、单独给予华法林或氯贝丁酯、或同时给予两种药物的情况下，将特异性标记的[3H]维生素K静脉注射给四名健康志愿者。单独使用氯贝丁酯不影响氚化维生素K的代谢。单独使用华法林会使大量维生素K环氧化物在血浆中蓄积，维生素K环氧化物是维生素K的一种代谢产物，可通过一种特异性还原酶再转化为维生素K。虽然再转化在很大程度上显然被华法林阻断，但在有华法林存在的情况下，氚化维生素K在血浆中的消失情况几乎与未用药时观察到的情况重叠。同时给予氯贝丁酯并未导致血浆中维生素K环氧化物的蓄积增加。这些结果表明，氯贝丁酯不会增强对还原酶的抑制作用。对氚化维生素K血浆消失数据的分析表明，体内维生素K的池大小较小，且每天周转近10次。维生素K环氧化物数据表明，在未用药的情况下，相对较小比例的环氧化物会再转化为维生素。
