Pharmacokinetic Profile of A New Diclofenac Prodrug without Gastroulcerogenic Effect

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dc.contributor.authorde Campos, Michel Leandro [UNESP]
dc.contributor.authorBaldan-Cimatti, Helen Mariana [UNESP]
dc.contributor.authorDavanço, Marcelo Gomes [UNESP]
dc.contributor.authorNogueira, Marco Antônio Ferraz [UNESP]
dc.contributor.authorPadilha, Elias Carvalho [UNESP]
dc.contributor.authorCandido, Caroline Damico [UNESP]
dc.contributor.authordos Santos, Jean Leandro [UNESP]
dc.contributor.authorPeccinini, Rosangela Goncalves [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-27T11:28:36Z
dc.date.available2014-05-27T11:28:36Z
dc.date.issued2013-03-01
dc.description.abstractGastrotoxicity is a major problem for long-term therapy with non-steroidal anti-inflammatory drugs (NSAIDs). DICCIC (1-(2,6-dichlorophenyl)indolin-2-one) is a new diclofenac prodrug, which has proven anti-inflammatory activity without gastroulcerogenic effect. The aim of this work was to compare the pharmacokinetic profiles of diclofenac from DICCIC (7.6 mg/kg equivalent to 8.1 mg/kg diclofenac) and diclofenac (8.1 mg/kg) administration in Wistar rats weighing 250-300 g (n=20). The doses were calculated by interspecific allometric scaling based on the 2 mg/kg from diary human dose of diclofenac. Blood samples were collected in heparinized tubes via the femoral artery through the implanted catheter. The plasma was separated and quantitation was made in a HPLC system with a UV-Vis detector. The confidence limits of the bioanalytical method were appropriate for its application in a preclinical pharmacokinetic study. The AUC of diclofenac from DICCIC (53.7± 5.8 ug/mL.min) was significantly less (Mann Whitney test, p<0.05) than that of diclofenac from diclofenac administration (885.9 ± 124,8 ug/mL.min). Terminal half-life of diclofenac from DICCIC (50.1 ± 17.2 min) was significantly less (Mann Whitney test, p<0.05) than that of diclofenac from diclofenac administration (247.4 ± 100.9 min). Still the parameters clearance and distribution volume were calculated for diclofenac from diclofenac, whose results were 9.2 ±1.2 mL/min.kg and 3.3 ±1.2 L/kg, respectively. The results of DICCIC from DICCIC administration were 108.9 ± 19.6 mL/min.kg and 7.8 ± 2.4 L/kg for clearance and distribution volume, respectively. The pharmacokinetic profile demonstrated that there was an increase in diclofenac elimination and a lower exposure to diclofenac with administration of DICCIC compared to diclofenac. © 2013 Bentham Science Publishers.en
dc.description.affiliationDepartamento de Princípios Ativos Naturais e Toxicologia Universidade Estadual Paulista - UNESP, Araraquara, SP
dc.description.affiliationLaboratório de Pesquisa e Desenvolvimento de Fármacos Departamento de Fármacos e Medicamentos Universidade Estadual Paulista - UNESP, Araraquara, SP
dc.description.affiliationUnespDepartamento de Princípios Ativos Naturais e Toxicologia Universidade Estadual Paulista - UNESP, Araraquara, SP
dc.description.affiliationUnespLaboratório de Pesquisa e Desenvolvimento de Fármacos Departamento de Fármacos e Medicamentos Universidade Estadual Paulista - UNESP, Araraquara, SP
dc.format.extent235-241
dc.identifierhttp://dx.doi.org/10.2174/1872312811206040002
dc.identifier.citationDrug Metabolism Letters, v. 6, n. 4, p. 235-241, 2013.
dc.identifier.doi10.2174/1872312811206040002
dc.identifier.issn1872-3128
dc.identifier.lattes1066743423929093
dc.identifier.scopus2-s2.0-84884239265
dc.identifier.urihttp://hdl.handle.net/11449/74754
dc.language.isoeng
dc.relation.ispartofDrug Metabolism Letters
dc.relation.ispartofsjr0,314
dc.rights.accessRightsAcesso restrito
dc.sourceScopus
dc.subject1-(2,6-dichlorophenyl)indolin-2-one
dc.subjectBioanalytical method
dc.subjectDiclofenac prodrug
dc.subjectPreclinical pharmacokinetic profile
dc.subject[1 (2,6 dichlorophenyl)indolin 2 one]
dc.subjectdiclofenac
dc.subjectdiclofenac derivative
dc.subjectprodrug
dc.subjectunclassified drug
dc.subjectallometry
dc.subjectanimal experiment
dc.subjectarea under the curve
dc.subjectcontrolled study
dc.subjectdistribution volume
dc.subjectdrug clearance
dc.subjectdrug determination
dc.subjectdrug distribution
dc.subjectdrug elimination
dc.subjectdrug exposure
dc.subjectdrug half life
dc.subjecthigh performance liquid chromatography
dc.subjectlimit of quantitation
dc.subjectmale
dc.subjectnonhuman
dc.subjectpharmaceutical equivalence
dc.subjectplasma concentration-time curve
dc.subjectpriority journal
dc.subjectrat
dc.titlePharmacokinetic Profile of A New Diclofenac Prodrug without Gastroulcerogenic Effecten
dc.typeArtigo
dcterms.licensehttp://eurekaselect.com/209
unesp.author.lattes1066743423929093
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências Farmacêuticas, Araraquarapt

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Artigos - Princípios Ativos Naturais e Toxicologia - FCFAR
Artigos - Fármacos e Medicamentos - FCFAR