Effects of combined treatment with cognitive enhancer memantine
and antidepressant fluoxetine on CYP2D2 metabolic activity in
rats

J 2011

Effects of combined treatment with cognitive enhancer memantine and antidepressant fluoxetine on CYP2D2 metabolic activity in rats

ZENDULKA, Ondřej; Jan JUŘICA; Lucia ZAHRADNÍKOVÁ; Michaela SABOVÁ; Alexandra ŠULCOVÁ et al.

Základní údaje

Originální název

Effects of combined treatment with cognitive enhancer memantine and antidepressant fluoxetine on CYP2D2 metabolic activity in rats

Název česky

Účinky kombinování kognitiva memantinu a antiderpesiva fluoxetinu na metabolickou aktivitu CYP2D6 u potkanů

Autoři

ZENDULKA, Ondřej; Jan JUŘICA; Lucia ZAHRADNÍKOVÁ; Michaela SABOVÁ a Alexandra ŠULCOVÁ

Vydání

Neuroendocrinology Letters, Sweden, Stockholm, Maghira and Maas Publications, 2011, 0172-780X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Švédsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 1.296

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/11:00055489

Organizační jednotka

Středoevropský technologický institut

UT WoS

000300543900026

Klíčová slova česky

cytochrom P450;memantin; fluoxetin; potkan; inhibice

Klíčová slova anglicky

cytochrome P450; memantine; fluoxetine; rat; inhibition

Štítky

ok, rivok

Příznaky

Mezinárodní význam

Změněno: 3. 4. 2012 09:53, doc. PharmDr. Ondřej Zendulka, Ph.D.

Anotace

ORIG CZ

V originále

The drug-drug interactions can result in alterations of the therapeutical responses. The present study was designed to investigate possible pharmacokinetic interactions between the cognitive agent memantine and the antidepressant fluoxetine combined often in treatments of cognitive disorders including Alzheimer disease. The attention was focused on changes of the cytochrome P450 2D2 isoenzyme activity in two animal models. METHODS AND DESIGN: The tested drugs were administered alone or in a combination to rat males and their effects on the 2D2 isoenzyme activity was determined after in vivo administration. The levels of marker dextromethorphan, its 2D2 specific metabolite dextrorphan were analyzed in plasma of rats and using the model of isolated perfused rat liver in the perfusion medium. The dextromethorphan/ dextrorphan (DEM/DEX) metabolic ratios were determined as a sign of inhibitory influences on CYP2D2. RESULTS: The analyses showed elevation of DEM/DEX metabolic ratio after all treatments: a) memantine, b) fluoxetine and c) memantine+fluoxetine, however the results were not completely identical. The intensity of inhibitory effects on the CYP2D2 activity were: memantine < memantine + fluoxetine < fluoxetine. CONCLUSION: The results presented suggest that the clinical pharmacotherapeutical approach to combine memantine with fluoxetine is from the point of view of pharmacokinetic drug-drug interaction on the level of CYP2D2 isoenzyme safe and even of benefit as memantine could elicit a suppression of the inhibitory influence of fluoxetine.

Česky

Výsledky studie naznačují, že farmakoterapie kombinací memantinu a fluoxetinu je z pohledu farmakokinetické interakce na úrovni izoenzymu CYP2D2 bezpečná a může snižovat inhibiční účinky fluoxetinu.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

MSM0021622404, záměr

Název: Vnitřní organizace a neurobiologické mechanismy funkčních systémů CNS

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Vnitřní organizace a neurobiologické mechanismy funkčních systémů CNS

Citovat

ZENDULKA, Ondřej; Jan JUŘICA; Lucia ZAHRADNÍKOVÁ; Michaela SABOVÁ a Alexandra ŠULCOVÁ. Effects of combined treatment with cognitive enhancer memantine and antidepressant fluoxetine on CYP2D2 metabolic activity in rats. Neuroendocrinology Letters. Sweden, Stockholm: Maghira and Maas Publications, 2011, roč. 32, č. 5, s. 727–732. ISSN 0172-780X.

@article{970491,
   author = {Zendulka, Ondřej and Juřica, Jan and Zahradníková, Lucia and Sabová, Michaela and Šulcová, Alexandra},
   article_location = {Sweden, Stockholm},
   article_number = {5},
   keywords = {cytochrome P450; memantine; fluoxetine; rat; inhibition},
   language = {eng},
   issn = {0172-780X},
   journal = {Neuroendocrinology Letters},
   title = {Effects of combined treatment with cognitive enhancer memantine and antidepressant fluoxetine on CYP2D2 metabolic activity in rats},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/22167136},
   volume = {32},
   year = {2011}
}

TY  - JOUR
ID  - 970491
AU  - Zendulka, Ondřej - Juřica, Jan - Zahradníková, Lucia - Sabová, Michaela - Šulcová, Alexandra
PY  - 2011
TI  - Effects of combined treatment with cognitive enhancer memantine and antidepressant fluoxetine on CYP2D2 metabolic activity in rats
JF  - Neuroendocrinology Letters
VL  - 32
IS  - 5
SP  - 727–732
EP  - 727–732
PB  - Maghira and Maas Publications
SN  - 0172780X
KW  - cytochrome P450
KW  - memantine
KW  - fluoxetine
KW  - rat
KW  - inhibition
UR  - http://www.ncbi.nlm.nih.gov/pubmed/22167136
L2  - http://www.ncbi.nlm.nih.gov/pubmed/22167136
N2  - The drug-drug interactions can result in alterations of the therapeutical responses. The present study was designed to investigate possible pharmacokinetic interactions between the cognitive agent memantine and the antidepressant fluoxetine combined often in treatments of cognitive disorders including Alzheimer disease. The attention was focused on changes of the cytochrome P450 2D2 isoenzyme activity in two animal models. METHODS AND DESIGN: The tested drugs were administered alone or in a combination to rat males and their effects on the 2D2 isoenzyme activity was determined after in vivo administration. The levels of marker dextromethorphan, its 2D2 specific metabolite dextrorphan were analyzed in plasma of rats and using the model of isolated perfused rat liver in the perfusion medium. The dextromethorphan/ dextrorphan (DEM/DEX) metabolic ratios were determined as a sign of inhibitory influences on CYP2D2. RESULTS: The analyses showed elevation of DEM/DEX metabolic ratio after all treatments: a) memantine, b) fluoxetine and c) memantine+fluoxetine, however the results were not completely identical. The intensity of inhibitory effects on the CYP2D2 activity were: memantine < memantine + fluoxetine < fluoxetine. CONCLUSION: The results presented suggest that the clinical pharmacotherapeutical approach to combine memantine with fluoxetine is from the point of view of pharmacokinetic drug-drug interaction on the level of CYP2D2 isoenzyme safe and even of benefit as memantine could elicit a suppression of the inhibitory influence of fluoxetine.
ER  -

ZENDULKA, Ondřej; Jan JUŘICA; Lucia ZAHRADNÍKOVÁ; Michaela SABOVÁ a Alexandra ŠULCOVÁ. Effects of combined treatment with cognitive enhancer memantine and antidepressant fluoxetine on CYP2D2 metabolic activity in rats. \textit{Neuroendocrinology Letters}. Sweden, Stockholm: Maghira and Maas Publications, 2011, roč.~32, č.~5, s.~727–732. ISSN~0172-780X.

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