Comparative effects of H2-receptor antagonists on drug interaction in rats.
The most widely used H2-receptor antagonist, cimetidine, is known to interact with cytochrome P-450 drug-metabolizing enzymes and, therefore, interacts with other drugs which may be administered concurrently. In this study, effects of three H2-receptor antagonists, famotidine, ranitidine, and L-643,441, on drug interaction were studied using cimetidine as a positive control. Cimetidine and L-643,441, but not famotidine or ranitidine, prolonged antipyrine elimination and hexobarbital-induced sleeping time. The effect of cimetidine and famotidine on the anticoagulant effect on warfarin in rats was also investigated. Pretreatment of rats with cimetidine produced a significant depression of plasma prothrombin complex activity, whereas concomitant administration of famotidine did not alter the plasma prothrombin complex activity. Whereas cimetidine is known to impair the elimination of a number of drugs metabolized by microsomal mixed function oxidase enzyme systems, the results of the present study suggest that famotidine and ranitidine have little effect on these enzyme systems.
D000818:Animals; D000983:Antipyrine / Q000378:metabolism*; D002927:Cimetidine / Q000494:pharmacology; D004347:Drug Interactions; D015738:Famotidine; D006591:Hexobarbital / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects; D013830:Thiadiazoles / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014859:Warfarin / Q000494:pharmacology*
D006635:Histamine H2 Antagonists; D013830:Thiadiazoles; D013844:Thiazoles; D014859:Warfarin; D015738:Famotidine; C037400:L 643441; D002927:Cimetidine; D011899:Ranitidine; D006591:Hexobarbital; D000983:Antipyrine