Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment

Autores
Ceballos, Laura; Alvarez, Luis Ignacio; Moreno Torrejon, Laura; Lanusse, Carlos Edmundo
Año de publicación
2007
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The altered drug influx/efflux and enhanced metabolic capacity identified in triclabendazole (TCBZ)-resistant Fasciola hepatica contributes to the development of resistance to TCBZ. The aim of this work was to evaluate the pharmacokinetics (PK) and clinical efficacy (CE) of TCBZ administered alone or co-administered with ivermectin (IVM, drug efflux inhibitor) and methimazole (MTZ, metabolic inhibitor) in TCBZ-resistant F. hepatica parasitized sheep. Sheep infected with TCBZ-resistant F. hepatica were divided into three groups (n= 4): untreated control, TCBZ-treated and TCBZ+IVM+MTZ treated sheep. Plasma samples were collected (PK study) and analysed by HPLC. In the CE study, the animals were sacrificed at 15 days post-treatment to evaluate the comparative efficacy against TCBZ-resistant F. hepatica. The presence of IVM and MTZ did not affect the plasma PK behaviour of TCBZ metabolites. The combined drug treatment was not sufficient to enhance the poor efficacy of TCBZ against resistant F. hepatica. Finally, the enhancement of TCBZ concentrations in F. hepatica induced by both IVM and MTZ in ex vivo assays, did not reach a measurable effect under the current in vivo experimental conditions.
Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Moreno Torrejon, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
XXXIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental
Ciudad Autónoma de Buenos Aires
Argentina
Sociedad Argentina de Farmacología Experimental
Materia
Triclabendazole
Hepatica
Fasciola
Resistant
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:11336/268501
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatmentCeballos, LauraAlvarez, Luis IgnacioMoreno Torrejon, LauraLanusse, Carlos EdmundoTriclabendazoleHepaticaFasciolaResistanthttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4The altered drug influx/efflux and enhanced metabolic capacity identified in triclabendazole (TCBZ)-resistant Fasciola hepatica contributes to the development of resistance to TCBZ. The aim of this work was to evaluate the pharmacokinetics (PK) and clinical efficacy (CE) of TCBZ administered alone or co-administered with ivermectin (IVM, drug efflux inhibitor) and methimazole (MTZ, metabolic inhibitor) in TCBZ-resistant F. hepatica parasitized sheep. Sheep infected with TCBZ-resistant F. hepatica were divided into three groups (n= 4): untreated control, TCBZ-treated and TCBZ+IVM+MTZ treated sheep. Plasma samples were collected (PK study) and analysed by HPLC. In the CE study, the animals were sacrificed at 15 days post-treatment to evaluate the comparative efficacy against TCBZ-resistant F. hepatica. The presence of IVM and MTZ did not affect the plasma PK behaviour of TCBZ metabolites. The combined drug treatment was not sufficient to enhance the poor efficacy of TCBZ against resistant F. hepatica. Finally, the enhancement of TCBZ concentrations in F. hepatica induced by both IVM and MTZ in ex vivo assays, did not reach a measurable effect under the current in vivo experimental conditions.Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Moreno Torrejon, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaXXXIX Reunión Anual de la Sociedad Argentina de Farmacología ExperimentalCiudad Autónoma de Buenos AiresArgentinaSociedad Argentina de Farmacología ExperimentalSociedad Argentina de Farmacología Experimental2007info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/mswordapplication/pdfhttp://hdl.handle.net/11336/268501Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment; XXXIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; Ciudad Autónoma de Buenos Aires; Argentina; 2007; 64-64CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://aafeargentina.org/congresos-aafe/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:03:33Zoai:ri.conicet.gov.ar:11336/268501instacron: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:34982025-09-29 10:03:33.657CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment
title Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment
spellingShingle Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment
Ceballos, Laura
Triclabendazole
Hepatica
Fasciola
Resistant
title_short Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment
title_full Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment
title_fullStr Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment
title_full_unstemmed Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment
title_sort Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment
dc.creator.none.fl_str_mv Ceballos, Laura
Alvarez, Luis Ignacio
Moreno Torrejon, Laura
Lanusse, Carlos Edmundo
author Ceballos, Laura
author_facet Ceballos, Laura
Alvarez, Luis Ignacio
Moreno Torrejon, Laura
Lanusse, Carlos Edmundo
author_role author
author2 Alvarez, Luis Ignacio
Moreno Torrejon, Laura
Lanusse, Carlos Edmundo
author2_role author
author
author
dc.subject.none.fl_str_mv Triclabendazole
Hepatica
Fasciola
Resistant
topic Triclabendazole
Hepatica
Fasciola
Resistant
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv The altered drug influx/efflux and enhanced metabolic capacity identified in triclabendazole (TCBZ)-resistant Fasciola hepatica contributes to the development of resistance to TCBZ. The aim of this work was to evaluate the pharmacokinetics (PK) and clinical efficacy (CE) of TCBZ administered alone or co-administered with ivermectin (IVM, drug efflux inhibitor) and methimazole (MTZ, metabolic inhibitor) in TCBZ-resistant F. hepatica parasitized sheep. Sheep infected with TCBZ-resistant F. hepatica were divided into three groups (n= 4): untreated control, TCBZ-treated and TCBZ+IVM+MTZ treated sheep. Plasma samples were collected (PK study) and analysed by HPLC. In the CE study, the animals were sacrificed at 15 days post-treatment to evaluate the comparative efficacy against TCBZ-resistant F. hepatica. The presence of IVM and MTZ did not affect the plasma PK behaviour of TCBZ metabolites. The combined drug treatment was not sufficient to enhance the poor efficacy of TCBZ against resistant F. hepatica. Finally, the enhancement of TCBZ concentrations in F. hepatica induced by both IVM and MTZ in ex vivo assays, did not reach a measurable effect under the current in vivo experimental conditions.
Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Moreno Torrejon, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
XXXIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental
Ciudad Autónoma de Buenos Aires
Argentina
Sociedad Argentina de Farmacología Experimental
description The altered drug influx/efflux and enhanced metabolic capacity identified in triclabendazole (TCBZ)-resistant Fasciola hepatica contributes to the development of resistance to TCBZ. The aim of this work was to evaluate the pharmacokinetics (PK) and clinical efficacy (CE) of TCBZ administered alone or co-administered with ivermectin (IVM, drug efflux inhibitor) and methimazole (MTZ, metabolic inhibitor) in TCBZ-resistant F. hepatica parasitized sheep. Sheep infected with TCBZ-resistant F. hepatica were divided into three groups (n= 4): untreated control, TCBZ-treated and TCBZ+IVM+MTZ treated sheep. Plasma samples were collected (PK study) and analysed by HPLC. In the CE study, the animals were sacrificed at 15 days post-treatment to evaluate the comparative efficacy against TCBZ-resistant F. hepatica. The presence of IVM and MTZ did not affect the plasma PK behaviour of TCBZ metabolites. The combined drug treatment was not sufficient to enhance the poor efficacy of TCBZ against resistant F. hepatica. Finally, the enhancement of TCBZ concentrations in F. hepatica induced by both IVM and MTZ in ex vivo assays, did not reach a measurable effect under the current in vivo experimental conditions.
publishDate 2007
dc.date.none.fl_str_mv 2007
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/268501
Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment; XXXIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; Ciudad Autónoma de Buenos Aires; Argentina; 2007; 64-64
CONICET Digital
CONICET
url http://hdl.handle.net/11336/268501
identifier_str_mv Triclabendazole resistant fasciola hepatica: pharmacokimetic and efficacy assessments of a drug combined treatment; XXXIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; Ciudad Autónoma de Buenos Aires; Argentina; 2007; 64-64
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://aafeargentina.org/congresos-aafe/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/msword
application/pdf
dc.publisher.none.fl_str_mv Sociedad Argentina de Farmacología Experimental
publisher.none.fl_str_mv Sociedad Argentina de Farmacología Experimental
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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