Dynamic interaction between disulfiram and separated enantiomorphs of racemic warfarin.

Abstract

To evaluate the interaction of disulfiram with the separated enantiomorphs of racemic warfarin, seven normal subjects received single doses of R-warfarin (1.5 mg/kg body weight) and S-warfarin (0.75 mg/kg body weight) with and without a daily dose of disulfiram 250 mg, beginning 3 days before the warfarin dose and continuing for the duration of the hypoprothrombinemia. Disulfiram augmented the S-warfarin hypoprothrombinemia (p less than 0.001) but not that of R-warfarin (p less than 0.10). Disulfiram did not alter plasma concentrations of either R-warfarin (p greater than 0.10) or S-warfarin (p greater than 0.40). Disulfiram augments the hypoprothrombinemia of racemic warfarin stereoselectively by interacting primarily with S-warfarin. As disulfiram did not change the plasma concentrations of either enantiomorph, it may augment the anticoagulant effect of racemic warfarin by directly affecting the hepatic mechanism responsible for the hypoprothrombinemia.