Enantioselective in vitro metabolism and in vitro-in vivo correlation of the herbicide ethofumesate in a human model

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.creatorPerovani, Icaro Salgado-
Autor(es): dc.creatorCarrão, Daniel Blascke-
Autor(es): dc.creatorde Albuquerque, Nayara Cristina Perez-
Autor(es): dc.creatorde Oliveira, Anderson Rodrigo Moraes [UNESP]-
Data de aceite: dc.date.accessioned2022-02-22T00:25:36Z-
Data de disponibilização: dc.date.available2022-02-22T00:25:36Z-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-08-05-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.jpba.2020.113349-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/198818-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/198818-
Descrição: dc.descriptionEthofumesate (ETO) is a chiral herbicide that is marketed as a racemic mixture in the European Union and the United States. The growing consumption of pesticides in the world, along with their presence in water and food, has increased human exposure to these chemicals. Another issue concerning these compounds is that each enantiomer of a chiral pesticide may interact with biomolecules differently. For this reason, this study aimed to investigate the in vitro metabolism of ethofumesate (the racemic mixture as well as the isolated enantiomers) by human liver microsomes (HLM) and to explore the in vitro-in vivo correlation. Before the kinetics was determined, the method was fully validated by evaluating its selectivity, linearity, precision, accuracy, carryover, and stability. All the evaluated parameters agreed with the European Medicines Agency guideline. The enzyme kinetic parameters and the in vitro-in vivo correlation demonstrated that there was no enantioselective difference for the metabolism and bioavailable fraction of each enantiomer. The enzyme kinetics was biphasic; the KM1 values were 15, 5.8, and 5.6 for rac-ETO, (+)-ETO, and (–)-ETO, respectively. The total in vitro intrinsic clearance was 0.10 mg mL min−1 mg−1 for rac-ETO and its enantiomers. The enantiomer (–)-ETO was only metabolized by CYP2C19, while (+)-ETO was metabolized by both CYP2C19 and CYP3A4. CYP2C19 polymorphism and/or inhibition may represent a risk for humans exposed to this pesticide.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionDepartamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo-
Descrição: dc.descriptionNational Institute for Alternative Technologies of Detection Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT–DATREM) Unesp Institute of Chemistry, P.O. Box 355-
Descrição: dc.descriptionNational Institute for Alternative Technologies of Detection Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT–DATREM) Unesp Institute of Chemistry, P.O. Box 355-
Descrição: dc.descriptionFAPESP: 2014/50945-4-
Descrição: dc.descriptionFAPESP: 2018/07534-4-
Descrição: dc.descriptionCNPq: 465571/2014-0-
Idioma: dc.languageen-
Relação: dc.relationJournal of Pharmaceutical and Biomedical Analysis-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectenantioselective in vitro metabolism-
Palavras-chave: dc.subjectethofumesate-
Palavras-chave: dc.subjectGC-MS-
Palavras-chave: dc.subjectHerbicide-
Palavras-chave: dc.subjecthuman liver microsomes-
Palavras-chave: dc.subjectin vitro-in vivo correlation-
Título: dc.titleEnantioselective in vitro metabolism and in vitro-in vivo correlation of the herbicide ethofumesate in a human model-
Tipo de arquivo: dc.typelivro digital-
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