No effect of the new antidepressant reboxetine on CYP2D6 activity in healthy volunteers
| Autor: | Angela Avenoso, Maria Gabriella Scordo, Gabriella Facciolà, Edoardo Spina |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Male CYP2D6 animal structures Time Factors Morpholines Pharmacology Dextromethorphan Reboxetine Dextrorphan medicine Humans Pharmacology (medical) Drug Interactions Enzyme Inhibitors Volunteer Cross-Over Studies Chemistry Drug interaction Paroxetine Antidepressive Agents Isoenzymes Phenotype Cytochrome P-450 CYP2D6 Female Reuptake inhibitor medicine.drug |
| Zdroj: | Therapeutic drug monitoring. 21(5) |
| ISSN: | 0163-4356 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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