STUDIES ON THE COUMARIN ANTICOAGULANT DRUGS: THE PHARMACODYNAMICS OF WARFARIN IN MAN*

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Abstract
The metabolism of warfarin in man was studied with a spectro-photometric method recently developed in this laboratory. A standard dose of warfarin (1.5 mg/kg) was administered orally to 14 normal subjects. Maximal concetions in plasma occurred in 2 to 12 hours. The half-time of warfarin''s disappearance from the plasma had a mean of 42 hours. Maximal depression of prothrombin complex activity was achieved between 36 and 72 hours. High degrees of correlation were found between the plasma concentrations of warfarin at 48, 72, and 96 hours and the degree of prothrombin complex depression. The absorption of warfarin from the gastrointestinal tract appeared to be complete, since no warfarin was found in the stool even after massive oral doses. The apparent volume of distribution was the same size as the albumin space. Oral administration of vitamin K1 did not influence the rates of absorption or chemical transformation of warfarin.