Effect of warfarin and the chloro analog of vitamin K 1 on phylloquinone metabolism

Abstract

The effect of a coumarin anticoagulant, warfarin, and of 2-chloro-3-phytyl-1,4-naphthoquinone (chloro K) on the distribution of radioactive phylloquinone (vitamin K 1) has been studied in the rat. Warfarin administration did not influence the whole body distribution of a dose of 3 or 5 μg of radioactive phylloquinone per 100 g of body weight, nor did it affect the subcellular distribution of liver radioactivity. Administration of the chloro analog of vitamin K 1 caused a 2- to 3-fold increase in the amount of radioactivity from the injected vitamin which was found in the liver. Most of this increase was shown to be in the mitochondrial fraction of liver. The data suggest that the chloro analog interferes with the metabolism of phylloquinone in the liver, and that much of the increased liver phylloquinone is then retained in the mitochondria. These effects on distribution of the vitamin should be considered in any attempt to explain the mechanism by which the chloro analog of vitamin K acts as an anticoagulant.