Reduction of enantioselectivity in the kinetic disposition and metabolism of verapamil in rats exposed to toluene

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dc.contributor.authorMateus, F. H.
dc.contributor.authorLepera, José Salvador [UNESP]
dc.contributor.authorMarques, M. P.
dc.contributor.authorBoralli, V. B.
dc.contributor.authorLanchote, V. L.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-20T13:25:32Z
dc.date.available2014-05-20T13:25:32Z
dc.date.issued2008-05-01
dc.description.abstractToluene and verapamil are subject to extensive oxidative metabolism mediated by CYP enzymes, and their interaction can be stereoselective. In the present study we investigated the influence of toluene inhalation on the enantioselective kinetic disposition of verapamil and its metabolite, norverapamil, in rats. Male Wistar rats (n = 6 per group) received a single dose of racemic verapamil (10 mg/kg) orally at the fifth day of nose-only toluene or air (control group) inhalation for 6 h/day (25, 50, and 100 ppm). Serial blood samples were collected from the tail up to 6 h after verapamil administration. The plasma concentrations of verapamil and norverapamil enantiomers were analyzed by LC-MS/MS by using a Chiralpak AD column. Toluene inhalation did not influence the kinetic disposition of verapamil or norverapamil enantiomers (p > 0.05, Kruskal-Wallis test) in rats. The pharmacokinetics of verapamil was enantioselective in the control group, with a higher plasma proportion of the S-verapamil (AUC 250.8 versus 120.4 ng.h.mL(-1); p <= 0.05, Wilcoxon test) and S-norverapamil (AUC 72.3 versus 52.3 ng.h.mL(-1); p <= 0.05, Wilcoxon test). Nose-only exposure to toluene at 25, 50, or 100 ppm resulted in a lack of enantioselectivity for both verapamil and norverapamil. The study demonstrates the importance of the application of enantioselective methods in studies on the interaction between solvents and chiral drugs.en
dc.description.affiliationUniv São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-05508 São Paulo, Brazil
dc.description.affiliationUniv Estadual Paulista, Fac Ciencias Farmaceut Araraquara, Dept Principios Ativos Nat & Toxicol, São Paulo, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Fac Ciencias Farmaceut Araraquara, Dept Principios Ativos Nat & Toxicol, São Paulo, Brazil
dc.format.extent232-239
dc.identifierhttp://dx.doi.org/10.1139/Y08-017
dc.identifier.citationCanadian Journal of Physiology and Pharmacology. Ottawa: Canadian Science Publishing, Nrc Research Press, v. 86, n. 5, p. 232-239, 2008.
dc.identifier.doi10.1139/Y08-017
dc.identifier.issn0008-4212
dc.identifier.lattes6710074203174471
dc.identifier.urihttp://hdl.handle.net/11449/8101
dc.identifier.wosWOS:000256626200002
dc.language.isoeng
dc.publisherCanadian Science Publishing, Nrc Research Press
dc.relation.ispartofCanadian Journal of Physiology and Pharmacology
dc.relation.ispartofjcr2.210
dc.relation.ispartofsjr0,724
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectverapamilen
dc.subjectpharmacokineticsen
dc.subjecttolueneen
dc.subjectnose-only exposureen
dc.subjectCYPen
dc.subjectratsen
dc.titleReduction of enantioselectivity in the kinetic disposition and metabolism of verapamil in rats exposed to tolueneen
dc.typeArtigo
dcterms.licensehttp://www.nrcresearchpress.com/page/authors/information/rights
dcterms.rightsHolderCanadian Science Publishing, Nrc Research Press
unesp.author.lattes6710074203174471
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências Farmacêuticas, Araraquarapt

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Artigos - Princípios Ativos Naturais e Toxicologia - FCFAR