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 cyto chrome P450 (CYP) 2D6 isoenzyme was investigated in 10 healthy volunteers u sing dextromethorphan as a model CYP2D6 substrate. Each volunteer received a single 30 mg oral dose of dextromethorphan on three different occasions s eparated by an interval of at least 4 weeks: a) in a control session; b) af ter 1 week of treatment with reboxetine, 8 mg/day; and c) after 1 week of t reatment with paroxetine tan inhibitor of CYP2D6 activity) 20 mg/day. Urine was collected over the next 8 hours for the determination of the dextromet horphan/dextrorphan metabolic ratio. All subjects were classified as extens ive 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, th ere 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.