Inhibition of Tolbutamide Elimination by Cimetidine but not Ranitidine

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.