RACEMIC WARFARIN AND TRIMETHOPRIM-SULFAMETHOXAZOLE INTERACTION IN HUMANS

Normal humans (11) were studied to evaluate the reported interaction of the anticoagulants racemic sodium warfarin and trimethoprim-sulfamethoxazole prospectively. Single oral doses of racemic warfarin, 1.5 mg/kg body wt, were administered with and without 320 mg of trimethoprim and 1600 mg of sulfamethoxazole orally beginning 7 d (day) before the warfarin and continuing daily throughout the hypoprothrombinemia. Daily plasma samples were analyzed for 1-stage prothrombin activity (Quick) and for warfarin content by high-pressure liquid chromatography. Transient cutaneous reactions developed in 4 of 11 subjects: a morbilliform rash in 3 (studies discontinued) and generalized pruritus in 1. A highly significant augmentation of the warfarin effect on the mean 1-stage prothrombin activity (P < 0.003) occurred with trimethoprim-sulfamethoxazole but no significant effect was found on the warfarin half-life (P > 0.5). Apparently trimethoprim-sulfamethoxazole interacts with racemic warfarin possibly at a receptor-site locus.