Interaction of Sodium Warfarin and Disulfiram (Antabuse®) in Man

To evaluate the interaction of sodium warfarin and disulfiram (Antabuse®), a single dose (1.5 mg/kg body weight) and a 21-day course of sodium warfarin were administered orally, with and without disulfiram orally, to eight normal subjects. A significant augmentation of both the hypoprothrombinemia (P < 0.01) and the plasma warfarin level (P < 0.05) occurred with daily disulfiram compared with warfarin alone, for both the single-dose and 21-day experiments. In the single-dose and 21-day experiments a highly significant correlation of the changes in plasma warfarin levels and in the hypoprothrombinemia occurred, which was positive in 13 and negative in 2 experiments. We conclude that disulfiram increases the anticoagulant effect of warfarin therapy in most but not all subjects by inhibiting its metabolism in the liver. An augmentation of the therapeutic effect of a drug by disulfiram has thus been shown for the first time in humans.