VITAMIN-K METABOLISM AND VITAMIN-K1 STATUS IN HUMAN LIVER SAMPLES - ASEARCH FOR INTERINDIVIDUAL DIFFERENCES IN WARFARIN SENSITIVITY

Vitamin K-dependent parameters in human liver samples were investigate d to find a clue to the inter-individual differences in sensitivity fo r oral anticoagulants. Vitamin K epoxide reductase and vitamin K-depen dent carboxylase activity differed 2-3-fold between the samples. Micro somal warfarin binding correlated significantly with the reductase act ivity. Microsomal vitamin K epoxide reductase of the different samples showed equal sensitivity for warfarin inhibition. 150 about 0.1 muM. Vitamin K epoxide reductase activity stimulated by NADH/lipoamide and microsomal lipoamide dehydrogenase activity showed higher inter-subjec t variability than the reductase activity by itself. Liver vitamin K1 levels varied 4-5-fold. Total and liver microsomal vitamin K1 levels w ere correlated. One of the liver samples was obtained from a donor ant icoagulated with phenprocoumon and additionally treated with vitamin K 1. High levels of the vitamin and its epoxide were present. Phenprocou mon was essentially irreversibly bound to the microsomes. In general t he results confirm inter-individual differences in the hepatic vitamin K-dependent systems; the differences as such were found to be small. However. as the various parameters can work synergisticatly in the sam e direction, they may well account for the wide dose range observed in oral anticoagulant therapy.