EFFECTS OF CLOFIBRATE AND WARFARIN ALONE AND IN COMBINATION ON THE DISPOSITION OF VITAMIN-K1

  • 1 January 1979
    • journal article
    • research article
    • Vol. 210  (3) , 322-326
Abstract
Clofibrate [antilipemic] may interact with warfarin [anticoagulant] by potentiating its effects on vitamin K disposition. Specifically labeled [3H]vitamin K was given i.v. to 4 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 [3H] vitamin K. Warfarin alone produced an accumulation in plasma of substantial amounts of vitamin K epoxide, a metabolite of vitamin K, reconverted to vitamin K by a specific reductase. Although reconversion was apparently blocked to a large extent by warfarin, the plasma disappearance of [3H] vitamin K in the presence of warfarin was almost superimposable to that observed in the absence of drugs. Clofibrate coadministration did not result in greater accumulation of vitamin K epoxide in plasma. Clofibrate apparently did not enhance the inhibition of the reductase enzyme. Analysis of the [3H] vitamin K plasma disappearance data indicated that the pool size of vitamin K in the body was small, and was turned over almost 10 times daily. The vitamin K epoxide data suggested that, in the absence of drugs, a relatively small proportion of the epoxide was reconverted to the vitamin.