Abstract
Abstract This randomized, four-way crossover study in 16 healthy subjects compared the effects of cimetidine 800 mg, ranitidine 300 mg and omeprazole 40 mg against placebo given daily after breakfast for seven days on the pharmacokinetics of a single oral dose of tolbutamide (500 mg) given on day 4. Plasma tolbutamide and urinary hydroxytolbutamide and carboxytolbutamide concentrations were determined by HPLC. Ranitidine had no significant effects on tolbutamide metabolism. Cimetidine produced a 20% increase in AUC (P < 0·001) and a 14% increase in t 1/2 (P < 0·01), while omeprazole produced a 10% increase in AUC (P < 001). The effect of these agents on urinary concentrations of the tolbutamide metabolites was small. These results do not indicate that interactions of major clinical significance occur in healthy subjects.
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