The effect of pyrazinamide and rifampicin on isoniazid metabolism in rats

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dc.contributor.authorDe Rosa, Helene J.
dc.contributor.authorBaldan, Helen M.
dc.contributor.authorBrunetti, Iguatemy Lourenço [UNESP]
dc.contributor.authorXimenes, Valdecir Farias [UNESP]
dc.contributor.authorMachado, Rosangela G. P.
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-20T13:24:34Z
dc.date.available2014-05-20T13:24:34Z
dc.date.issued2007-09-01
dc.description.abstractHepatotoxicity is the main concern during tuberculosis chemotherapy with the first-line drugs isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR). Since these hepatotoxic events have been associated with INH metabolites, the study aimed to measure the area under curve (AUC) parameter for INH and its metabolites acetylisoniazid (AcINH), hydrazine (Hz) and acetylhydrazine (AcHz), when groups of rats were pre-treated for 21 days with INH alone or in combination with RMP and/or PYR, in the following amounts per kg body weight: INH 100 mg; INH 100 mg + RMP 100 mg; INH 100 mg + PYR 350 mg; INH 100 mg + PYR 350 mg + RMP 100 mg. It was found that co-administration of RMP, PYR and RMP + PYR caused a significant decrease in the AUC for INH. Co-administration of PYR was the only treatment that caused a significant increase in the AUC for Hz and a decrease in the AUC for its acetylated product AcHz. The AUC for AcINH was not significantly altered in any experimental group. In conclusion, the increased metabolism of INH in all the drug combinations and the significantly higher production of Hz in the group INH + PYR might be linked with exacerbated hepatotoxic effects of these drug associations. Copyright (c) 2007 John Wiley & Sons, Ltd.en
dc.description.affiliationUniv Estadual Paulista, Dept Principios Ativos Nat & Toxicol, Araraquara, SP, Brazil
dc.description.affiliationUniv Estadual Paulista, Fac Ciências Farmaceut, Dept Analises Clin, Araraquara, SP, Brazil
dc.description.affiliationUniv Estadual Paulista, Fac Ciências, Dept Quim, Bauru, SP, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Dept Principios Ativos Nat & Toxicol, Araraquara, SP, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Fac Ciências Farmaceut, Dept Analises Clin, Araraquara, SP, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Fac Ciências, Dept Quim, Bauru, SP, Brazil
dc.format.extent291-296
dc.identifierhttp://dx.doi.org/10.1002/bdd.557
dc.identifier.citationBiopharmaceutics & Drug Disposition. Chichester: John Wiley & Sons Ltd, v. 28, n. 6, p. 291-296, 2007.
dc.identifier.doi10.1002/bdd.557
dc.identifier.issn0142-2782
dc.identifier.lattes4066413997908572
dc.identifier.urihttp://hdl.handle.net/11449/7660
dc.identifier.wosWOS:000249836800004
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofBiopharmaceutics & Drug Disposition
dc.relation.ispartofjcr1.677
dc.relation.ispartofsjr0,551
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectisoniazidpt
dc.subjectrifampicinpt
dc.subjectpyrazinamidept
dc.subjectacetylisoniazidpt
dc.subjectacetylhydrazinept
dc.titleThe effect of pyrazinamide and rifampicin on isoniazid metabolism in ratsen
dc.typeArtigo
dcterms.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dcterms.rightsHolderWiley-Blackwell
unesp.author.lattes4066413997908572
unesp.author.orcid0000-0003-2636-3080[4]
unesp.author.orcid0000-0003-4927-7599[3]
unesp.author.orcid0000-0002-2692-8101[5]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências Farmacêuticas, Araraquarapt
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências, Baurupt

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Artigos - Princípios Ativos Naturais e Toxicologia - FCFAR
Artigos - Análises Clínicas - FCFAR
Artigos - Química - FC