Impact of inhalational exposure to ethanol fuel on the pharmacokinetics of verapamil, ibuprofen and fluoxetine as in vivo probe drugs for CYP3A, CYP2C and CYP2D in rats.

Occupational toxicology and clinical pharmacology integration will be useful to understand potential exposure-drug interaction and to shape risk assessment strategies in order to improve occupational health. The aim of the present study was to evaluate the effect of exposure to ethanol fuel on in vivo activities of cytochrome P450 (CYP) isoenzymes CYP3A, CYP2C and CYP2D by the oral administration of the probe drugs verapamil, ibuprofen and fluoxetine. Male Wistar rats exposed to filtered air or to 2000 ppm ethanol in a nose-only inhalation chamber during (6 h/day, 5 days/week, 6 weeks) received single oral doses of 10 mg/kg verapamil or 25 mg/kg ibuprofen or 10 mg/kg fluoxetine.

Analysis of ibuprofen enantiomers in rat plasma by liquid chromatography with tandem mass spectrometry.

A sensitive and selective method for the analysis of ibuprofen enantiomers by LC-MS/MS was developed and validated for the purpose of application in pharmacokinetic studies in small experimental animals. Aliquots of 200 μL plasma were submitted to liquid-liquid extraction with hexane/diisopropylether (50:50 v/v) in acid pH. Separation was accomplished in a Chirex® 3005 (250 × 4.

Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats.

Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition.