title: No effect of the new antidepressant reboxetine on CYP2D6 activity in healthy volunteers.
abstract: The effect of the new antidepressant reboxetine on the activity of the cytochrome P450 (CYP) 2D6 isoenzyme was investigated in 10 healthy volunteers using dextromethorphan as a model CYP2D6 substrate. Each volunteer received a single 30 mg oral dose of dextromethorphan on three different occasions separated by an interval of at least 4 weeks: a) in a control session; b) after 1 week of treatment with reboxetine, 8 mg/day; and c) after 1 week of treatment with paroxetine (an inhibitor of CYP2D6 activity) 20 mg/day. Urine was collected over the next 8 hours for the determination of the dextromethorphan/dextrorphan metabolic ratio. All subjects were classified as extensive metabolizers (EM) with a dextromethorphan/dextrorphan ratio < 0.3. There were no notable changes in the urinary dextromethorphan/dextrorphan ratio in the reboxetine phase as compared to the control session. By contrast, there was a statistically significant increase in the metabolic ratio in the paroxetine phase (p < 0.001), with 4 subjects switching to poor metabolizer (PM) phenotype. These results suggest that reboxetine is unlikely to cause clinically significant interactions with substrates of CYP2D6.
authors.affiliation: Institute of Pharmacology, University of Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Avenoso
authors.forename: G
authors.initials: G
authors.lastname: Facciolà
authors.forename: M G
authors.initials: MG
authors.lastname: Scordo
authors.forename: E
authors.initials: E
authors.lastname: Spina
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology*; D018592:Cross-Over Studies; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D003915:Dextromethorphan / Q000494:pharmacology / Q000652:urine; D003917:Dextrorphan / Q000652:urine; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007527:Isoenzymes; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D017374:Paroxetine / Q000494:pharmacology*; D010641:Phenotype; D000077593:Reboxetine; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009025:Morpholines; D003917:Dextrorphan; D017374:Paroxetine; D003915:Dextromethorphan; D000077593:Reboxetine; D019389:Cytochrome P-450 CYP2D6