Dynamic interaction between disulfiram and separated enantiomorphs of racemic warfarin.
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.
D000328:Adult; D004221:Disulfiram / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D008297:Male; D011517:Prothrombin Time; D013237:Stereoisomerism; D014859:Warfarin / Q000378:metabolism*
D014859:Warfarin; D004221:Disulfiram