No effect of the new antidepressant reboxetine on CYP2D6 activity in healthy volunteers.
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.
Avenoso
A
A
Institute of Pharmacology, University of Messina, Italy.
Facciolà
G
G
Scordo
M G
MG
Spina
E
E
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
D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009025:Morpholines; D003917:Dextrorphan; D017374:Paroxetine; D003915:Dextromethorphan; D000077593:Reboxetine; D019389:Cytochrome P-450 CYP2D6