title: Inhibition of dextromethorphan metabolism by moclobemide.
abstract: This pilot study was conducted to evaluate the potential of the new antidepressant moclobemide to inhibit the cytochrome enzyme P4502D6 (CYP2D6) using the cough suppressant dextromethorphan as a substrate in four extensive metabolizers (EM) of debrisoquine. The subjects received seven oral doses of 20 mg dextromethorphan at 4-h intervals over 2 days (1 and 2) and subsequently moclobemide (300 mg b.i.d.) for 9 days. On days 10 and 11, they received seven doses of 20 mg dextromethorphan in addition to moclobemide. During monotreatment and combined treatment, blood was collected on days 2 and 11, respectively, for determination of dextromethorphan and its demethylated metabolites using automated high-performance liquid chromatography with column switching. Concurrent administration of moclobemide markedly reduced the O-demethylation of dextromethorphan, whereas the N-demethylation of dextrorphan to hydroxymorphinan was not affected. The findings indicate that moclobemide can affect the pharmacokinetics of drugs that are mainly metabolized by CYP2D6.
authors.affiliation: Department of Psychiatry, University of Mainz, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Härtter
authors.forename: J
authors.initials: J
authors.lastname: Dingemanse
authors.forename: D
authors.initials: D
authors.lastname: Baier
authors.forename: G
authors.initials: G
authors.lastname: Ziegler
authors.forename: C
authors.initials: C
authors.lastname: Hiemke
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001549:Benzamides / Q000494:pharmacology*; D001711:Biotransformation; D003915:Dextromethorphan / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D003915:Dextromethorphan; D020912:Moclobemide