TY - JOUR T1 - Comparative effects of H2-receptor antagonists on drug interaction in rats. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 649 LP - 653 VL - 14 IS - 6 AU - J H Lin AU - D M Cocchetto AU - K C Yeh AU - D E Duggan Y1 - 1986/11/01 UR - http://dmd.aspetjournals.org/content/14/6/649.abstract N2 - 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. ER -