Dynamics and persistence of CYP2D6 inhibition by paroxetine

J 2013

Dynamics and persistence of CYP2D6 inhibition by paroxetine

JUŘICA, Jan a Alexandra ŽOURKOVÁ

Základní údaje

Originální název

Dynamics and persistence of CYP2D6 inhibition by paroxetine

Autoři

JUŘICA, Jan (203 Česká republika, garant, domácí) a Alexandra ŽOURKOVÁ (203 Česká republika, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 1.533

Kód RIV

RIV/00216224:14740/13:00065968

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1111/jcpt.12042

UT WoS

000321339800006

Klíčová slova anglicky

CYP2D6; disinhibition; paroxetine

Štítky

ok, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 10. 12. 2013 10:21, Olga Křížová

Anotace

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.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

GAP206/10/0057, projekt VaV

Název: Miniaturizovaný systém pro "on-line" studie metabolismu léčiv založený na kapilární elektroforéze

Investor: Grantová agentura ČR, Miniaturizovaný systém pro "on-line" studie metabolismu léčiv založený na kapilární elektroforéze

Citovat

JUŘICA, Jan a Alexandra ŽOURKOVÁ. Dynamics and persistence of CYP2D6 inhibition by paroxetine. JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS. HOBOKEN: WILEY-BLACKWELL, 2013, roč. 38, č. 4, s. 294-300. ISSN 0269-4727. Dostupné z: https://dx.doi.org/10.1111/jcpt.12042.

@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 a Alexandra ŽOURKOVÁ. Dynamics and persistence of CYP2D6 inhibition by paroxetine. \textit{JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS}. HOBOKEN: WILEY-BLACKWELL, 2013, roč.~38, č.~4, s.~294-300. ISSN~0269-4727. Dostupné z: https://dx.doi.org/10.1111/jcpt.12042.

Podrobný výpis o publikaci