Decreased oral warfarin clearance after ranitidine and cimetidine.

Oxidative metabolism inhibition of a number of drugs by cimetidine has been attributed to its imidazole ring, a hypothesis that has been supported by reports that ranitidine does not affect drug metabolism despite being five times as potent as cimetidine as an H2-receptor antagonist. In five healthy subjects ranitidine at 150 mg twice daily induced a 27% fall in apparent oral warfarin clearance. In the same subjects cimetidine at 1 gm/day induced a 36% decrease in warfarin clearance. In two of the subjects the experiment was repeated after giving 750 mg ranitidine per day and in two other subjects after 200 mg cimetidine twice daily. In both instances there was a stepwise fall in warfarin clearance with increasing doses. The data indicate that interference with drug metabolism by H2-receptor antagonists is not confined to cimetidine but that on a molar basis ranitidine and cimetidine are roughly equivalent in inhibiting warfarin clearance and that the effects are related to dose.