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@article{1078052,
author = {Juřica, Jan and Žourková, Alexandra},
article_location = {HOBOKEN},
article_number = {4},
doi = {http://dx.doi.org/10.1111/jcpt.12042},
keywords = {CYP2D6; disinhibition; paroxetine},
language = {eng},
issn = {0269-4727},
journal = {JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS},
title = {Dynamics and persistence of CYP2D6 inhibition by paroxetine},
url = {http://onlinelibrary.wiley.com/doi/10.1111/jcpt.12042/abstract},
volume = {38},
year = {2013}
}
TY - JOUR
ID - 1078052
AU - Juřica, Jan - Žourková, Alexandra
PY - 2013
TI - Dynamics and persistence of CYP2D6 inhibition by paroxetine
JF - JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
VL - 38
IS - 4
SP - 294-300
EP - 294-300
PB - WILEY-BLACKWELL
SN - 02694727
KW - CYP2D6
KW - disinhibition
KW - paroxetine
UR - http://onlinelibrary.wiley.com/doi/10.1111/jcpt.12042/abstract
L2 - http://onlinelibrary.wiley.com/doi/10.1111/jcpt.12042/abstract
N2 - 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.
ER -
JUŘICA, Jan and Alexandra ŽOURKOVÁ. Dynamics and persistence of CYP2D6 inhibition by paroxetine. \textit{JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS}. HOBOKEN: WILEY-BLACKWELL, 2013, vol.~38, No~4, p.~294-300. ISSN~0269-4727. Available from: https://dx.doi.org/10.1111/jcpt.12042.
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