Ranitidine at very large doses does not inhibit theophylline elimination

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Abstract
While most controlled studies in humans indicate that ranitidine does not alter drug metabolism, there is some evidence that ranitidine may have this property. If ranitidine does not inhibit drug metabolism in a predictable manner, such an effect might be expressed at higher ranitidine doses. Our study was designed to contrast the effects of large doses of ranitidine (1200 and 4200 mg/day) and cimetidine (1200 mg/day) on the theophylline elimination. Whereas cimetidine decreased theophylline clearance in 11 of 12 subjects by a mean of 19.4%, neither ranitidine dose affected theophylline disposition. While case reports indicate ranitidine may inhibit theophylline metabolism specifically and drug metabolism in general, we were not able in our controlled study to detect any effect of ranitidine on theophylline elimination even at ranitidine doses up to fourteenfold greater than are generally prescribed.