Racemic warfarin and trimethoprim-sulfamethoxazole interaction in humans.
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 less than 0.03) occurred with trimethoprim-sulfamethoxazole, but no significant effect was found on the warfarin half-life (P greater than 0.5). It is concluded that trimethoprim-sulfamethoxazole interacts with racemic warfarin, possibly at a receptor-site locus.
D000328:Adult; D004338:Drug Combinations; D004347:Drug Interactions; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011517:Prothrombin Time; D013420:Sulfamethoxazole / Q000494:pharmacology*; D014295:Trimethoprim / Q000494:pharmacology*; D014859:Warfarin / Q000097:blood / Q000494:pharmacology*
D004338:Drug Combinations; D014859:Warfarin; D014295:Trimethoprim; D013420:Sulfamethoxazole