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A comparative study of the effects of warfarin and brodifacoum on the relationship between vitamin K1, metabolism and clotting factor activity in warfarin-susceptible and warfarin-resistant rats

1981; Elsevier BV; Volume: 30; Issue: 2 Linguagem: Inglês

10.1016/0006-2952(81)90182-9

1873-2968

Jacqueline B. Leck, B.Kevin Park,

Animal Ecology and Behavior Studies

The effects of the anticoagulants warfarin and brodifacoum on [3H]vitamin K1 metabolism and clotting factor activity were studied in warfarin-susceptible and warfarin-resistant rats. Brodifacoum produced the same rate of degradation of prothrombin complex activity (PCA) as warfarin in the rat and significantly reduced the activity of clotting factors, II, VII, IX and X but did not affect factor V. Metabolic studies using [3H]vitamin K1 showed that brodifacoum increased the hepatic concentration ratio of [3H]vitamin K1 epoxide: [3H]vitamin K1 in both warfarin-susceptible and warfarin-resistant rats at doses which produced anticoagulation. Brodifacoum produced a significant increase in the rate of excretion of [3H]vitamin K1 metabolites in bile but did not affect the urinary excretion of [3H]vitamin K1 metabolites. The results indicate that brodifacoum has the same mechanism of action as warfarin and support the concept that coumarin anticoagulants reduce vitamin K1-dependent clotting factor synthesis by interrupting the vitamin K1-epoxide cycle.