Racemic Warfarin and Trimethoprim-Sulfamethoxazole Interaction in Humans

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

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