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Dynamic interaction between disulfiram and separated enantiomorphs of racemic warfarin
Author(s) -
O'Reilly Robert A
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.45
Subject(s) - hypoprothrombinemia , warfarin , disulfiram , prothrombin time , pharmacology , medicine , drug interaction , anticoagulant , chemistry , anesthesia , pharmacokinetics , atrial fibrillation , vitamin k
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 < 0.001) but not that of R‐warfarin (p > 0.10). Disulfiram did not alter plasma concentrations of either R‐warfarin (p > 0.10) or S‐warfarin (p > 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. Clinical Pharmacology and Therapeutics (1981) 29, 332–336; doi: 10.1038/clpt.1981.45