Inhibition of Tolbutamide Elimination by Cimetidine but not Ranitidine

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Abstract
This study was designed to compare the effects of equivalent therapeutic doses of two H2 antagonists, cimetidine and ranitidine, on tolbutamide pharmacokinetics. Twelve healthy men were given a 1‐g oral dose of tolbutamide on three occasions. Subjects were randomly assigned to three treatments in a crossover fashion: cimetidine 1,200 mg/d, ranitidine 300 mg/d, and placebo. Cimetidine significantly increased the tolbutamide area under the plasma concentration‐time curve by 20% (range, −5% to 42%), increased the elimination half‐life by 17%, and decreased the carboxytolbutamide:tolbutamide plasma ratio from 0.042 to 0.036. Ranitidine did not significantly alter tolbutamide pharmacokinetics.

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