J 2013

Dynamics and persistence of CYP2D6 inhibition by paroxetine

JUŘICA, Jan and Alexandra ŽOURKOVÁ

Basic information

Original name

Dynamics and persistence of CYP2D6 inhibition by paroxetine

Authors

JUŘICA, Jan (203 Czech Republic, guarantor, belonging to the institution) and Alexandra ŽOURKOVÁ (203 Czech Republic, belonging to the institution)

Edition

JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS, HOBOKEN, WILEY-BLACKWELL, 2013, 0269-4727

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 1.533

RIV identification code

RIV/00216224:14740/13:00065968

Organization unit

Central European Institute of Technology

DOI

UT WoS

000321339800006

Keywords in English

CYP2D6; disinhibition; paroxetine

Tags

Tags

International impact, Reviewed
Změněno: 10/12/2013 10:21, Olga Křížová

Abstract

V originále

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.

Links

ED1.1.00/02.0068, research and development project
Name: CEITEC - central european institute of technology
GAP206/10/0057, research and development project
Name: Miniaturizovaný systém pro "on-line" studie metabolismu léčiv založený na kapilární elektroforéze
Investor: Czech Science Foundation, Miniaturized on-line drug metabolism system based on capillary electrophoresis