WHAT IS KNOWN AND OBJECTIVE: Paroxetine is both a substrate and an inhibitor of CYP2D6. The objective of the presented study was to determine the persistence of CYP2D6 inhibition after short term (6 weeks) and long term (18·7 ± 10·6 weeks) paroxetine treatment. METHODS: Two the studies consisted of 30 depressive/anxiety patients each. In the first study, patients were subdivided into three groups treated with paroxetine (A1), alprazolam (A2) and paroxetine + alprazolam (A3). After 6 weeks, all the patients (A1+A2+A3) were switched to alprazolam treatment; metabolic activity was evaluated at the beginning, after 6 weeks of paroxetine/alprazolam/alprazolam + paroxetine treatment (A1/A2/A3) and 4 weeks after the switch to alprazolam treatment (Week 0, 6, 10). In the second study patients on previous long term paroxetine treatment were subdivided into two groups treated with mirtazapine (B1) or paroxetine (B2); metabolic activity of CYP2D6 was evaluated at the beginning and after 6 weeks of therapy. RESULTS AND DISCUSSION: Metabolic ratio of dextromethorphan to dextrorphan has normalized in all subjects after 4 weeks of paroxetine wash out in the first study. In the second study, 6 weeks after paroxetine discontinuation, restoration of metabolic activity of CYP2D6 was observed in only five of eight originally poor metabolizers. WHAT IS NEW AND CONCLUSION: We conclude that a wash-out period of 4 weeks seems to be sufficient for CYP2D6 disinhibition after short-term paroxetine treatment (6 weeks). On the other hand, treatment with a CYP2D6 substrate less than 6 weeks after long-term paroxetine treatment (18·7 weeks on average) could result in elevated drug plasma levels and occasionally also in drug toxicity.
- MeSH
- alprazolam farmakologie MeSH
- cytochrom P-450 CYP2D6 metabolismus MeSH
- deprese farmakoterapie enzymologie metabolismus MeSH
- dextromethorfan farmakologie MeSH
- dextrorfan farmakologie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- inhibitory cytochromu P450 CYP2D6 MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- paroxetin farmakologie MeSH
- senioři MeSH
- úzkost farmakoterapie enzymologie metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- MeSH
- chování zvířat MeSH
- deprese enzymologie metabolismus patologie MeSH
- dřeň nadledvin enzymologie fyziologie MeSH
- fyziologický stres patologie MeSH
- kardiovaskulární fyziologické jevy MeSH
- kardiovaskulární systém MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
