Detailed Information on Publication Record
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.Basic information
Original name
Effects of combined treatment with cognitive enhancer memantine and antidepressant fluoxetine on CYP2D2 metabolic activity in rats
Name in Czech
Účinky kombinování kognitiva memantinu a antiderpesiva fluoxetinu na metabolickou aktivitu CYP2D6 u potkanů
Authors
ZENDULKA, Ondřej (203 Czech Republic, belonging to the institution), Jan JUŘICA (203 Czech Republic, belonging to the institution), Lucia ZAHRADNÍKOVÁ (203 Czech Republic, belonging to the institution), Michaela SABOVÁ (703 Slovakia, belonging to the institution) and Alexandra ŠULCOVÁ (203 Czech Republic, guarantor, belonging to the institution)
Edition
Neuroendocrinology Letters, Sweden, Stockholm, Maghira and Maas Publications, 2011, 0172-780X
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30104 Pharmacology and pharmacy
Country of publisher
Sweden
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 1.296
RIV identification code
RIV/00216224:14740/11:00055489
Organization unit
Central European Institute of Technology
UT WoS
000300543900026
Keywords (in Czech)
cytochrom P450;memantin; fluoxetin; potkan; inhibice
Keywords in English
cytochrome P450; memantine; fluoxetine; rat; inhibition
Tags
International impact
Změněno: 3/4/2012 09:53, doc. PharmDr. Ondřej Zendulka, Ph.D.
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.
In Czech
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.
Links
| ED1.1.00/02.0068, research and development project |
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| MSM0021622404, plan (intention) |
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