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dc.contributor.author
Maté, María Laura  
dc.contributor.author
Geary, T.  
dc.contributor.author
Mackenzie, C.  
dc.contributor.author
Lanusse, Carlos Edmundo  
dc.contributor.author
Virkel, Guillermo Leon  
dc.date.available
2018-09-06T12:40:06Z  
dc.date.issued
2017-10  
dc.identifier.citation
Maté, María Laura; Geary, T.; Mackenzie, C.; Lanusse, Carlos Edmundo; Virkel, Guillermo Leon; Species differences in hepatic biotransformation of the anthelmintic drug flubendazole; Wiley Blackwell Publishing, Inc; Journal of Veterinary Pharmacology and Therapeutics; 40; 5; 10-2017; 493-499  
dc.identifier.issn
0140-7783  
dc.identifier.uri
http://hdl.handle.net/11336/58484  
dc.description.abstract
Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic used in pigs, poultry, and humans. It has been proposed as a candidate for development for use in elimination programmes for lymphatic filariasis and onchocerciasis in humans. Moreover, FLBZ has shown promise in cancer chemotherapy, particularly for neuroblastoma. This work investigated the hepatic carbonyl-reducing pathway of FLBZ in different species, including humans. Microsomal and cytosolic fractions were obtained from sheep, cattle, pig, hen, rat, and human liver. Both subcellular fractions of each species converted FLBZ into a reduced metabolite (red-FLBZ). The rate of microsomal red-FLBZ production was highest in sheep (1.92 ± 0.13 nmol/min.mg) and lowest in pigs (0.04 ± 0.02 nmol/min.mg); cytosolic red-FLBZ production ranged from 0.02 ± 0.01 (pig) to 1.86 ± 0.61 nmol/min.mg (sheep). Only subcellular fractions from sheep liver oxidized red-FLBZ to FLBZ in a NADP+-dependent oxidative reaction. Liver microsomes from both pigs and humans transformed FLBZ to red-FLBZ and a hydrolyzed metabolite. Very significant differences in the pattern of FLBZ metabolism were observed among the tested species and humans. These results reinforce the need for caution in extrapolating data on metabolism, efficacy, and safety of drugs derived from studies performed in different species.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Wiley Blackwell Publishing, Inc  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Flubendazole  
dc.subject
Anthelmintics  
dc.subject
Biotransformation  
dc.subject
Species Differences  
dc.subject.classification
Otras Ciencias Veterinarias  
dc.subject.classification
Ciencias Veterinarias  
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CIENCIAS AGRÍCOLAS  
dc.title
Species differences in hepatic biotransformation of the anthelmintic drug flubendazole  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-09-05T16:11:28Z  
dc.journal.volume
40  
dc.journal.number
5  
dc.journal.pagination
493-499  
dc.journal.pais
Reino Unido  
dc.journal.ciudad
Londres  
dc.description.fil
Fil: Maté, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina  
dc.description.fil
Fil: Geary, T.. McGill University; Canadá  
dc.description.fil
Fil: Mackenzie, C.. Michigan State University; Estados Unidos  
dc.description.fil
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina  
dc.description.fil
Fil: Virkel, Guillermo Leon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina  
dc.journal.title
Journal of Veterinary Pharmacology and Therapeutics  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1111/jvp.12383  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/jvp.12383