STUDY OF THE EFFECT OF ANTICOAGULANTS ON [VITAMIN-K1-H-3 METABOLISM AND PROTHROMBIN COMPLEX ACTIVITY IN THE RABBIT

The effect of the anticoagulants warfarin, 2-chloro-3-phytyl- 1,4-naphthoquinone (Cl-K), acenocoumarol, brodifacoum and difenacoum on [3H]vitamin K1 metabolism and prothrombin complex activity (P.C.A.) were studied in the rabbit. All five anticoagulants inhibited clotting factor synthesis and the rate of decline of P.C.A. was similar for each drug. Metabolic studies with [3H]vitamin K1 showed that warfarin, acenocoumarol, brodifacoum and difenacoum increased the plasma ratio of [3H]vitamin K1 epoxide: [3H] vitamin K1 but that Cl-K decreased the ratio when compared with controls. None of the anticoagulants produced any significant change in the rate of disappearance of [3H]vitamin K1 from plasma. The results show that the metabolism of vitamin K1 and its relationship with P.C.A. are the same as in man. The effect of the anticoagulants on [3H]vitamin K1 metabolism are consistent with the concept that interruption of the vitamin K1 epoxide cycle, at either the epoxidase step or the reductase step, will result in a reduction in vitamin K1-dependent clotting factor synthesis. © 1979.