Dynamics and persistence of CYP2D6 inhibition by paroxetine
Article first published online: 26 FEB 2013
© 2013 John Wiley & Sons Ltd
Journal of Clinical Pharmacy and Therapeutics
Volume 38, Issue 4, pages 294–300, August 2013
How to Cite
Juřica, J. and Žourková, A. (2013), Dynamics and persistence of CYP2D6 inhibition by paroxetine. Journal of Clinical Pharmacy and Therapeutics, 38: 294–300. doi: 10.1111/jcpt.12042
- Issue published online: 6 JUL 2013
- Article first published online: 26 FEB 2013
- Manuscript Accepted: 6 DEC 2012
- Manuscript Received: 6 SEP 2012
- European Regional Development Fund . Grant Number: CZ.1·05/1·1·00/02·0068
- ‘CEITEC – Central European Institute of Technology’. Grant Numbers: P206/10/0057, CZ.1·05/1·1·00/02·0068
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.
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.