| Autor: |
Cardoso, Juciane Lauren Cavalcanti, Lanchote, Vera Lucia, Pereira, Maria Paula Marques, Capela, Jorge Manuel Vieira, Lepera, José Salvador |
| Zdroj: |
Chirality; Mar2013, Vol. 25 Issue 3, p206-210, 5p |
| Abstrakt: |
ABSTRACT is used clinically as a racemic mixture of (+)-( S) and (-)-( R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air ( n = 36; control group) or to 600 ppm of gasoline ( n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic . enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-( S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC(+)-( S)/(-)-( R) = 1.68). In animals exposed to gasoline, we observed an increase in AUC0-∞ for both enantiomers, with a sharper increase seen for the (-)-( R)-fluoxetine enantiomer (enantiomeric ratio AUC(+)-( S)/(-)-( R) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of , with the predominant reduction occurring in the clearance of the (-)-( R)-fluoxetine enantiomer (55% vs. 30%). Chirality 25:206-210, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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