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Influence of chronic exposure to automotive fuels in the activity of CYP3A, CYP2C9 and CYP2D in rats treated with chiral drugs

Abstract

Most frequently prescribed therapeutic agents are formulated and marketed in the racemic form, although for some, it has been demonstrated that the pharmacological and toxicological effects are associated only with one of the enantiomers. Moreover, it is well known that the enantiomers may have different pharmacokinetic and pharmacodynamic profiles. For the present study were selected drugs from three major groups in clinical use, which are verapamil, antihypertensive from group of antagonists of calcium channel, ibuprofen, from the group of nonsteroidal anti-inflammatory and fluoxetine, from the group of antidepressants. The study aims to evaluate the influence of chronic exposure to automotive fuel ethanol and gasoline in the stereoselective pharmacokinetics of these drugs. Male Wistar rats will be divided into 09 groups: control for verapamil, ibuprofen and fluoxetine; exposed to ethanol and verapamil, ibuprofen or fluoxetine, and exposed to gasoline and verapamil, ibuprofen, or fluoxetine. Exposure to fuels will be made in a nose only exposure chamber, for 6 hours / day, five days a week for 6 weeks. Pharmacokinetic analysis will be performed by compartmental modeling and first-order kinetics and group comparisons will be done by nonparametric statistical tests. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CAVALCANTI CARDOSO, JUCIANE LAUREN; LANCHOTE, VERA LUCIA; MARQUES PEREIRA, MARIA PAULA; VIEIRA CAPELA, JORGE MANUEL; LEPERA, JOSE SALVADOR. Influence of Gasoline Inhalation on the Enantioselective Pharmacokinetics of Fluoxetine in Rats. CHIRALITY, v. 25, n. 3, p. 206-210, . (09/17532-0)
CAVALCANTI CARDOSO, JUCIANE LAUREN; LANCHOTE, VERA LUCIA; MARQUES PEREIRA, MARIA PAULA; DE MORAES, NATALIA VALADARES; LEPERA, JOSE SALVADOR. Analysis of ibuprofen enantiomers in rat plasma by liquid chromatography with tandem mass spectrometry. JOURNAL OF SEPARATION SCIENCE, v. 37, n. 8, p. 944-949, . (09/17532-0)
CAVALCANTI CARDOSO, JUCIANE LAUREN; LANCHOTE, VERA LUCIA; MARQUES PEREIRA, MARIA PAULA; VIEIRA CAPELA, JORGE MANUEL; DE MORAES, NATALIA VALADARES; LEPERA, JOSE SALVADOR. 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. Food and Chemical Toxicology, v. 84, p. 99-105, . (09/17532-0)

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