Pharmacokinetic interaction between diltiazem and tolbutamide

The effect of co-administered tolbutamide and diltiazem on each drug's pharmacokinetics was studied in eight healthy male volunteers aged 21-25 years, with a 3 x 3 randomised crossover design. Each subject received orally 60 mg of diltiazem hydrochloride or 500 mg of tolbutamide, or both drugs. The washout period between each treatment was 7 days. Serum levels of diltiazem and tolbutamide were determined by HPLC. Serum profiles were analysed using a non-compartmental model. There was no change in the pharmacokinetics of diltiazem in the presence of tolbutamide. There was approximately 10% increase in AUC0-24 and Cmax for tolbutamide in the presence of diltiazem.