title: Lack of interaction between tolcapone and tolbutamide in healthy volunteers.
abstract: To assess the effect of tolcapone (an inhibitor of cytochrome P450 [CYP] 2C9 in vitro) on the pharmacokinetics and hypoglycemic effect of the CYP 2C9 substrate tolbutamide, 12 healthy male volunteers were randomized to receive a single dose of tolbutamide 500 mg plus either placebo or tolcapone 200 mg after an overnight fast and 30 minutes after the start of a 6.5-hour 5% glucose infusion (150 mL/h). The participants crossed over to receive the alternative regimen after a washout period 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.
authors.affiliation: Department of Research, F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: K M
authors.initials: KM
authors.lastname: Jorga
authors.forename: B
authors.initials: B
authors.lastname: Fotteler
authors.forename: R
authors.initials: R
authors.lastname: Gasser
authors.forename: L
authors.initials: L
authors.lastname: Banken
authors.forename: H
authors.initials: H
authors.lastname: Birnboeck
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D001577:Benzophenones / Q000009:adverse effects / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D005947:Glucose / Q000493:pharmacokinetics; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D009596:Nitrophenols; D016037:Single-Blind Method; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014044:Tolbutamide / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000077867:Tolcapone
chemical_list: D001577:Benzophenones; D001786:Blood Glucose; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D009596:Nitrophenols; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D000077867:Tolcapone; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; D005947:Glucose