Lack of interaction between tolcapone and tolbutamide in healthy volunteers

To assess the effect of tolcapone (an inhibitor of cytochrome [GYP] 2C9 in vitro) on the pharmacokinetics and hypo-glycemic effect of the GYP 2C9 substrate tolbutamide, 32 male volunteers were randomized to receive a single of tolbutamide 500 mg plus either placebo or tolcapone mg after an overnight fast and 30 minutes after the start 6.5-hour 5% glucose infusion (150 mL/h). The participants over to receive the alternative regimen after a washout of at least 7 days. Tolcapone had no effect on the pharmacokinetics of tolbutamide or its metabolites and did not influence the effect of tolbutamide on plasma glucose concentrations. No serious adverse events or abnormal laboratory results or vital signs were reported In conclusion, clinically relevant drug-drug interactions between tolcapone and tolbutamide when given together in clinical practice appear unlikely. (C) 2000 the American College of Clinical Pharmacology.