Lack of inhibition of tolbutamide hydroxylation by cimetidine in man.

We have investigated the influence of cimetidine on the disposition of tolbutamide in 7 healthy subjects, who received 250 mg tolbutamide daily for 4 days followed by the concomitant intake of cimetidine 400 mg twice daily for a further 4 days. Cimetidine had no effect on the disposition of tolbutamide, including the unbound hydroxylation clearance rate (324 ml X min-1, tolbutamide alone; 316 ml X min-1, tolbutamide plus cimetidine). The total urinary recovery of carboxy- and hydroxy-tolbutamide metabolites was 85.7 +/- 20.3% of the dose when tolbutamide was given alone and 78.9 +/- 14.3% when given with cimetidine. This lack of a pharmacokinetic interaction suggests selectivity of cimetidine-induced inhibition of Phase I drug oxidation.