VPLYV BUPROPIONU A POHLAVIA NA METABOLICKÚ AKTIVITU PEČEŇOVEJ IZOFORMY CYP2D2 V PREKLINICKOM EXPERIMENTE

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Title in English The influence of gender and administration of bupropion on the activity of hepatic CYP 450 2D2 in rats.
Authors

ZAHRADNÍKOVÁ Lucia ZENDULKA Ondřej JUŘICA Jan HADAŠOVÁ Eva

Year of publication 2006
Type Article in Proceedings
Conference Zborník prác 56. Farmakologické dni 2006 v Bratislave
MU Faculty or unit

Faculty of Medicine

Citation
Field Pharmacology and pharmaceutical chemistry
Keywords gender differencies; cytochrome P450; isolated perfused rat liver
Description One of the most important enzymatic systems participating in drug metabolism is cytochrome P 450 (CYP450). CYP 450 consists of many isoforms and its activity is influenced by numerous of endogenous (i.e. gender, physiological status, age) and exogenous factors (i.e. xenobiotical inhibitors and inducers). The aim of the present study was to determine the influence of gender and administration of antidepressant bupropion on the CYP 450 isoform 2D2 (CYP2D2). Bupropion and its metabolites are known as inhibitors of CYP2D6 in humans. Dextromethorphan (DEM) and its metabolite dextrorphane (DOR) were used as a selective markers of the metabolic activity of CYP2D2. The model of isolated perfused rat liver was used. Male and female Wistar rats (weighing 200-240g) were administered with saline or bupropion water solution i.p. for 10 days. The dose of bupropion was 2.2 mg/kg/day. Concentration of the selective marker DEM in perfusion medium ( Williams medium E) was 1mg/ml. The samples were collected in the 30th, 60th and 120th minute after addition of the marker. Levels of DEM and DOR were measured by HPLC method. Levels of DOR were higher in the 30th, 60th and 120th minute after addition of the marker in female rats than in male rats, indicating that the activity of CYP 450 2D2 was higher in female rats. The inhibitory effect of bupropion was expressed as a decrease of DOR in the 30th, 60th and 120th minute of perfusion in animals treated with bupropion compared to control animals administered with saline.
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