Changes in the urinary metabolites of phylloquinone (vitamin K1) in man following therapeutic anticoagulation with warfarin.

Abstract The metabolism of [1′,2-′ 3 H 2 ]phylloquinone was studied in five normal male volunteers both before and after treatment with therapeutic doses of warfarin for 8–10 days. Warfarin treatment caused an almost 2-fold increase in the urinary excretion of phylloquinone metabolites; a decrease in glucuronide conjugated metabolites and the excretion of an unidentified conjugate fraction resistant to hydrolysis by both β-glucuronidase and phenolsulphatase. In addition, excretion of the normal aglycones of phylloquinone was markedly reduced and was replaced by the excretion of more polar, hydroxylated metabolites which appeared to be derived from phylloquinone-2,3-epoxide. The results are consistent with the hypothesis that warfarin exerts its anticoagulant effect in man by blocking the regeneration of vitamin K from its 2,3-epoxide metabolite.