Repurposing oxfendazole as a potential flukicidal compound

Autores
Ceballos, Laura; Cantón, Candela; Dominguez, Maria Paula; Moreno Torrejon, Laura; Gayo, Valeria; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Oxfendazole (OFZ) is a nematodicidal drug without flukicidal activity at its recommended therapeutic dose in sheep (5 mg/kg). However, flukicidal activity has been described when OFZ was used at a higher dose (30 mg/kg) both in sheep and pigs. The goals of this study were to characterize the OFZ/metabolites plasma disposition kinetics after OFZ administration at either 5 (OFZ5) or 30 (OFZ30) mg/kg dose to non-infected sheep (PK study), and to evaluate the dose-related pattern of in vivo accumulation of OFZ/metabolites into F. hepatica (Accumulation study). Pk study: sheep (n=12) were orally treated with OFZ at either 5 (OFZTD) or 30 (OFZ30) mg/kg. Blood samples were collected over 96 h p.t. Accumulation study: F. hepatica infected animals (n=8) were orally treated with OFZ at either 5 or 30mg/kg. After sacrifice, samples of blood, bile, liver and adult liver flukes were obtained at different times. OFZ was the main analyte detected in plasma from OFZ treated sheep and its systemic exposure (AUC0?LOQ) increased from 17.9 ± 3.71 (OFZ5) up to 85.4 ± 22.6 (OFZ30) µg.h/mL. The Cmax value was 4-fold higher in the OFZ30 group than that in OFZ5 group. These differences were also reflected in the pattern of OFZ accumulation into F. hepatica, which was 332 % higher in group OFZ30 (4.28 µg/g) than OFZ5 (0.99 µg/g). The OFZ dose increment was clearly associated with a higher plasma drug exposure and accumulation into the F. hepatica, which help to explain the OFZ flukicidal efficacy observed after a dose of 30 mg/kg. The reported pharmacological data may contribute to assess OFZ repurposing for a new use as flukicidal.
Fil: Ceballos, 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
Fil: Cantón, Candela. 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
Fil: Dominguez, Maria Paula. 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
Fil: Moreno Torrejon, 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
Fil: Gayo, Valeria. No especifíca;
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
Fil: Alvarez, Luis Ignacio. 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
65º Annual Meeting American Association of Veterinary Parasitologists
Estados Unidos
American Association of Veterinary Parasitologists
Materia
Oxfendazole
Liver Fluke
Repurposing
Flukicidal compound
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/165501
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Repurposing oxfendazole as a potential flukicidal compoundCeballos, LauraCantón, CandelaDominguez, Maria PaulaMoreno Torrejon, LauraGayo, ValeriaLanusse, Carlos EdmundoAlvarez, Luis IgnacioOxfendazoleLiver FlukeRepurposingFlukicidal compoundhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4Oxfendazole (OFZ) is a nematodicidal drug without flukicidal activity at its recommended therapeutic dose in sheep (5 mg/kg). However, flukicidal activity has been described when OFZ was used at a higher dose (30 mg/kg) both in sheep and pigs. The goals of this study were to characterize the OFZ/metabolites plasma disposition kinetics after OFZ administration at either 5 (OFZ5) or 30 (OFZ30) mg/kg dose to non-infected sheep (PK study), and to evaluate the dose-related pattern of in vivo accumulation of OFZ/metabolites into F. hepatica (Accumulation study). Pk study: sheep (n=12) were orally treated with OFZ at either 5 (OFZTD) or 30 (OFZ30) mg/kg. Blood samples were collected over 96 h p.t. Accumulation study: F. hepatica infected animals (n=8) were orally treated with OFZ at either 5 or 30mg/kg. After sacrifice, samples of blood, bile, liver and adult liver flukes were obtained at different times. OFZ was the main analyte detected in plasma from OFZ treated sheep and its systemic exposure (AUC0?LOQ) increased from 17.9 ± 3.71 (OFZ5) up to 85.4 ± 22.6 (OFZ30) µg.h/mL. The Cmax value was 4-fold higher in the OFZ30 group than that in OFZ5 group. These differences were also reflected in the pattern of OFZ accumulation into F. hepatica, which was 332 % higher in group OFZ30 (4.28 µg/g) than OFZ5 (0.99 µg/g). The OFZ dose increment was clearly associated with a higher plasma drug exposure and accumulation into the F. hepatica, which help to explain the OFZ flukicidal efficacy observed after a dose of 30 mg/kg. The reported pharmacological data may contribute to assess OFZ repurposing for a new use as flukicidal.Fil: Ceballos, 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; ArgentinaFil: Cantón, Candela. 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; ArgentinaFil: Dominguez, Maria Paula. 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; ArgentinaFil: Moreno Torrejon, 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; ArgentinaFil: Gayo, Valeria. No especifíca;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; ArgentinaFil: Alvarez, Luis Ignacio. 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; Argentina65º Annual Meeting American Association of Veterinary ParasitologistsEstados UnidosAmerican Association of Veterinary ParasitologistsAmerican Association of Veterinary Parasitologists2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/165501Repurposing oxfendazole as a potential flukicidal compound; 65º Annual Meeting American Association of Veterinary Parasitologists; Estados Unidos; 2020; 140CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.aavp.org/aavp-2020-annual-meeting-2/info:eu-repo/semantics/altIdentifier/url/https://www.aavp.org/documents/2020/10/aavp-2020-annual-meeting-proceedings.pdf/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:54Zoai:ri.conicet.gov.ar:11336/165501instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:10:54.412CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Repurposing oxfendazole as a potential flukicidal compound
title Repurposing oxfendazole as a potential flukicidal compound
spellingShingle Repurposing oxfendazole as a potential flukicidal compound
Ceballos, Laura
Oxfendazole
Liver Fluke
Repurposing
Flukicidal compound
title_short Repurposing oxfendazole as a potential flukicidal compound
title_full Repurposing oxfendazole as a potential flukicidal compound
title_fullStr Repurposing oxfendazole as a potential flukicidal compound
title_full_unstemmed Repurposing oxfendazole as a potential flukicidal compound
title_sort Repurposing oxfendazole as a potential flukicidal compound
dc.creator.none.fl_str_mv Ceballos, Laura
Cantón, Candela
Dominguez, Maria Paula
Moreno Torrejon, Laura
Gayo, Valeria
Lanusse, Carlos Edmundo
Alvarez, Luis Ignacio
author Ceballos, Laura
author_facet Ceballos, Laura
Cantón, Candela
Dominguez, Maria Paula
Moreno Torrejon, Laura
Gayo, Valeria
Lanusse, Carlos Edmundo
Alvarez, Luis Ignacio
author_role author
author2 Cantón, Candela
Dominguez, Maria Paula
Moreno Torrejon, Laura
Gayo, Valeria
Lanusse, Carlos Edmundo
Alvarez, Luis Ignacio
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Oxfendazole
Liver Fluke
Repurposing
Flukicidal compound
topic Oxfendazole
Liver Fluke
Repurposing
Flukicidal compound
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv Oxfendazole (OFZ) is a nematodicidal drug without flukicidal activity at its recommended therapeutic dose in sheep (5 mg/kg). However, flukicidal activity has been described when OFZ was used at a higher dose (30 mg/kg) both in sheep and pigs. The goals of this study were to characterize the OFZ/metabolites plasma disposition kinetics after OFZ administration at either 5 (OFZ5) or 30 (OFZ30) mg/kg dose to non-infected sheep (PK study), and to evaluate the dose-related pattern of in vivo accumulation of OFZ/metabolites into F. hepatica (Accumulation study). Pk study: sheep (n=12) were orally treated with OFZ at either 5 (OFZTD) or 30 (OFZ30) mg/kg. Blood samples were collected over 96 h p.t. Accumulation study: F. hepatica infected animals (n=8) were orally treated with OFZ at either 5 or 30mg/kg. After sacrifice, samples of blood, bile, liver and adult liver flukes were obtained at different times. OFZ was the main analyte detected in plasma from OFZ treated sheep and its systemic exposure (AUC0?LOQ) increased from 17.9 ± 3.71 (OFZ5) up to 85.4 ± 22.6 (OFZ30) µg.h/mL. The Cmax value was 4-fold higher in the OFZ30 group than that in OFZ5 group. These differences were also reflected in the pattern of OFZ accumulation into F. hepatica, which was 332 % higher in group OFZ30 (4.28 µg/g) than OFZ5 (0.99 µg/g). The OFZ dose increment was clearly associated with a higher plasma drug exposure and accumulation into the F. hepatica, which help to explain the OFZ flukicidal efficacy observed after a dose of 30 mg/kg. The reported pharmacological data may contribute to assess OFZ repurposing for a new use as flukicidal.
Fil: Ceballos, 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
Fil: Cantón, Candela. 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
Fil: Dominguez, Maria Paula. 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
Fil: Moreno Torrejon, 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
Fil: Gayo, Valeria. No especifíca;
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
Fil: Alvarez, Luis Ignacio. 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
65º Annual Meeting American Association of Veterinary Parasitologists
Estados Unidos
American Association of Veterinary Parasitologists
description Oxfendazole (OFZ) is a nematodicidal drug without flukicidal activity at its recommended therapeutic dose in sheep (5 mg/kg). However, flukicidal activity has been described when OFZ was used at a higher dose (30 mg/kg) both in sheep and pigs. The goals of this study were to characterize the OFZ/metabolites plasma disposition kinetics after OFZ administration at either 5 (OFZ5) or 30 (OFZ30) mg/kg dose to non-infected sheep (PK study), and to evaluate the dose-related pattern of in vivo accumulation of OFZ/metabolites into F. hepatica (Accumulation study). Pk study: sheep (n=12) were orally treated with OFZ at either 5 (OFZTD) or 30 (OFZ30) mg/kg. Blood samples were collected over 96 h p.t. Accumulation study: F. hepatica infected animals (n=8) were orally treated with OFZ at either 5 or 30mg/kg. After sacrifice, samples of blood, bile, liver and adult liver flukes were obtained at different times. OFZ was the main analyte detected in plasma from OFZ treated sheep and its systemic exposure (AUC0?LOQ) increased from 17.9 ± 3.71 (OFZ5) up to 85.4 ± 22.6 (OFZ30) µg.h/mL. The Cmax value was 4-fold higher in the OFZ30 group than that in OFZ5 group. These differences were also reflected in the pattern of OFZ accumulation into F. hepatica, which was 332 % higher in group OFZ30 (4.28 µg/g) than OFZ5 (0.99 µg/g). The OFZ dose increment was clearly associated with a higher plasma drug exposure and accumulation into the F. hepatica, which help to explain the OFZ flukicidal efficacy observed after a dose of 30 mg/kg. The reported pharmacological data may contribute to assess OFZ repurposing for a new use as flukicidal.
publishDate 2020
dc.date.none.fl_str_mv 2020
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status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/165501
Repurposing oxfendazole as a potential flukicidal compound; 65º Annual Meeting American Association of Veterinary Parasitologists; Estados Unidos; 2020; 140
CONICET Digital
CONICET
url http://hdl.handle.net/11336/165501
identifier_str_mv Repurposing oxfendazole as a potential flukicidal compound; 65º Annual Meeting American Association of Veterinary Parasitologists; Estados Unidos; 2020; 140
CONICET Digital
CONICET
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language eng
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv American Association of Veterinary Parasitologists
publisher.none.fl_str_mv American Association of Veterinary Parasitologists
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