Effect of warfarin on the metabolism of phylloquinone (vitamin K1):dose-response relationships in man.

Summarg 1. The dose-response relationship between the oral anticoagulant, warfarin, and its effect on the metabolism of phylloquinone (vitamin K,) has been examined in normal male volunteer subjects. 2. In each study the subject received a single, oral dose of warfarin and, 2 h later, an intravenous injection of [l ',2'-3H2 Jphylloquinone. Changes in the metabolism of phylloquinone were assessed by thefractionation and chromatographic separation of labelled phylloquinone and its metabolites in plasma and urine samples. 3. Increasing doses of warfarin did not affect the rate of disappearance of injected phylloquinone from the plasma but caused the accumulation of increasing amounts of the metabolite, phylloquinone epoxide. 4. Increasing doses of warfarin were found to decrease the proportion of labelled conjugates excreted in the urine as glucuronides and to block progressively the excretion of the normal aglycones of phylloquinone. At the same time there was a progressive increase in the excre tion of at least three abnormal aglycones of phylloquinone. 5. The doses or plasma concentrations of warfarin were related to the increase in phylloquinone epoxide in the plasma and to the decrease in the proportion of normal aglycones of phylloquinone in urine by typical log dose-