Decreased oral warfarin clearance after ranitidine and cimetidine

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Abstract
Oxidative metabolism inhibition of a number of drugs by cimetidine is attributed to its imidazole ring, a hypothesis that is supported by reports that ranitidine does not affect drug metabolism despite being 5 times as potent as cimetidine as an H2-receptor antagonist. In 5 healthy subjects, ranitidine at 150 mg twice daily induced a 27% fall in apparent oral warfarin clearance. In the same subjects cimetidine at 1 g/day induced a 36% decrease in warfarin clearance. In 2 of the subjects, the experiment was repeated after giving 750 mg ranitidine/day and in 2 other subjects after 200 mg cimetidine twice daily. In both instances there was a stepwise fall in warfarin clearance with increasing doses. Interference with drug metabolism by H2-receptor antagonists is evidently not confined to cimetidine but on a molar basis, ranitidine and cimetidine are roughly equivalent in inhibiting warfarin clearance and the effects are related to dose.

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