Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice

Autores
Ceballos, Laura; Elissondo, María Celina; Sanchez Bruni, Sergio Fabian; Denegri, Guillermo Maria; Alvarez, Luis Ignacio; Lanusse, Carlos Edmundo
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cystic echinococcosis (CE) caused by the parasite Echinococcus granulosus is an important public health problem worldwide. Flubendazole has shown poor in vivo efficacy against CE in humans and mice. However, flubendazole causes marked in vitro damage on E. granulosus protoscoleces. The goals of the current work were: a) to compare the plasma pharmacokinetic behaviour of flubendazole formulated as a hydroxipropyl-β-cyclodextrin aqueous solution or as a carboxymethyl celullose suspension, both given by the oral route to mice, b) to compare flubendazole clinical efficacy in secondary CE in mice after its administration as both formulations, c) to evaluate the flubendazole-induced morphological changes in hydatid cysts recovered from infected mice treated with both drug formulations. Flubendazole administration as a solution resulted in significantly higher plasma maximum concentration (Cmax) and area under the concentration-time curve (AUC) values compared to those obtained after the flubendazole-suspension treatment. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the flubendazole-solution formulation, while the suspension formulation did not reach differences with the untreated control group. Similar ultrastructural changes were observed in cysts recovered from flubendazole (both formulations) treated mice after 3, 6 and 9 months of infection, although the damage extension was greater after treatment with the flubendazole-solution formulation.
Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina
Fil: Elissondo, María Celina. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina
Fil: Sanchez Bruni, Sergio Fabian. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Denegri, Guillermo Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; Argentina
Fil: Alvarez, Luis Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lanusse, Carlos Edmundo. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Cyclodextrins
Cystic Echinococcosis
Flubendazole
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:11336/82059
Acceder
id CONICETDig_adaaccdc8a3ea157bcc40987d108e512
oai_identifier_str oai:ri.conicet.gov.ar:11336/82059
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in miceCeballos, LauraElissondo, María CelinaSanchez Bruni, Sergio FabianDenegri, Guillermo MariaAlvarez, Luis IgnacioLanusse, Carlos EdmundoCyclodextrinsCystic EchinococcosisFlubendazolehttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4Cystic echinococcosis (CE) caused by the parasite Echinococcus granulosus is an important public health problem worldwide. Flubendazole has shown poor in vivo efficacy against CE in humans and mice. However, flubendazole causes marked in vitro damage on E. granulosus protoscoleces. The goals of the current work were: a) to compare the plasma pharmacokinetic behaviour of flubendazole formulated as a hydroxipropyl-β-cyclodextrin aqueous solution or as a carboxymethyl celullose suspension, both given by the oral route to mice, b) to compare flubendazole clinical efficacy in secondary CE in mice after its administration as both formulations, c) to evaluate the flubendazole-induced morphological changes in hydatid cysts recovered from infected mice treated with both drug formulations. Flubendazole administration as a solution resulted in significantly higher plasma maximum concentration (Cmax) and area under the concentration-time curve (AUC) values compared to those obtained after the flubendazole-suspension treatment. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the flubendazole-solution formulation, while the suspension formulation did not reach differences with the untreated control group. Similar ultrastructural changes were observed in cysts recovered from flubendazole (both formulations) treated mice after 3, 6 and 9 months of infection, although the damage extension was greater after treatment with the flubendazole-solution formulation.Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Elissondo, María Celina. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Sanchez Bruni, Sergio Fabian. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Denegri, Guillermo Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; ArgentinaFil: Alvarez, Luis Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lanusse, Carlos Edmundo. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Ireland2009-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/82059Ceballos, Laura; Elissondo, María Celina; Sanchez Bruni, Sergio Fabian; Denegri, Guillermo Maria; Alvarez, Luis Ignacio; et al.; Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice; Elsevier Ireland; Parasitology International; 58; 4; 12-2009; 354-3581383-5769CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.parint.2009.07.006info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:33Zoai:ri.conicet.gov.ar:11336/82059instacron: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 09:57:34.208CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice
title Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice
spellingShingle Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice
Ceballos, Laura
Cyclodextrins
Cystic Echinococcosis
Flubendazole
title_short Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice
title_full Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice
title_fullStr Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice
title_full_unstemmed Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice
title_sort Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice
dc.creator.none.fl_str_mv Ceballos, Laura
Elissondo, María Celina
Sanchez Bruni, Sergio Fabian
Denegri, Guillermo Maria
Alvarez, Luis Ignacio
Lanusse, Carlos Edmundo
author Ceballos, Laura
author_facet Ceballos, Laura
Elissondo, María Celina
Sanchez Bruni, Sergio Fabian
Denegri, Guillermo Maria
Alvarez, Luis Ignacio
Lanusse, Carlos Edmundo
author_role author
author2 Elissondo, María Celina
Sanchez Bruni, Sergio Fabian
Denegri, Guillermo Maria
Alvarez, Luis Ignacio
Lanusse, Carlos Edmundo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cyclodextrins
Cystic Echinococcosis
Flubendazole
topic Cyclodextrins
Cystic Echinococcosis
Flubendazole
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv Cystic echinococcosis (CE) caused by the parasite Echinococcus granulosus is an important public health problem worldwide. Flubendazole has shown poor in vivo efficacy against CE in humans and mice. However, flubendazole causes marked in vitro damage on E. granulosus protoscoleces. The goals of the current work were: a) to compare the plasma pharmacokinetic behaviour of flubendazole formulated as a hydroxipropyl-β-cyclodextrin aqueous solution or as a carboxymethyl celullose suspension, both given by the oral route to mice, b) to compare flubendazole clinical efficacy in secondary CE in mice after its administration as both formulations, c) to evaluate the flubendazole-induced morphological changes in hydatid cysts recovered from infected mice treated with both drug formulations. Flubendazole administration as a solution resulted in significantly higher plasma maximum concentration (Cmax) and area under the concentration-time curve (AUC) values compared to those obtained after the flubendazole-suspension treatment. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the flubendazole-solution formulation, while the suspension formulation did not reach differences with the untreated control group. Similar ultrastructural changes were observed in cysts recovered from flubendazole (both formulations) treated mice after 3, 6 and 9 months of infection, although the damage extension was greater after treatment with the flubendazole-solution formulation.
Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina
Fil: Elissondo, María Celina. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina
Fil: Sanchez Bruni, Sergio Fabian. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Denegri, Guillermo Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; Argentina
Fil: Alvarez, Luis Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lanusse, Carlos Edmundo. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Cystic echinococcosis (CE) caused by the parasite Echinococcus granulosus is an important public health problem worldwide. Flubendazole has shown poor in vivo efficacy against CE in humans and mice. However, flubendazole causes marked in vitro damage on E. granulosus protoscoleces. The goals of the current work were: a) to compare the plasma pharmacokinetic behaviour of flubendazole formulated as a hydroxipropyl-β-cyclodextrin aqueous solution or as a carboxymethyl celullose suspension, both given by the oral route to mice, b) to compare flubendazole clinical efficacy in secondary CE in mice after its administration as both formulations, c) to evaluate the flubendazole-induced morphological changes in hydatid cysts recovered from infected mice treated with both drug formulations. Flubendazole administration as a solution resulted in significantly higher plasma maximum concentration (Cmax) and area under the concentration-time curve (AUC) values compared to those obtained after the flubendazole-suspension treatment. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the flubendazole-solution formulation, while the suspension formulation did not reach differences with the untreated control group. Similar ultrastructural changes were observed in cysts recovered from flubendazole (both formulations) treated mice after 3, 6 and 9 months of infection, although the damage extension was greater after treatment with the flubendazole-solution formulation.
publishDate 2009
dc.date.none.fl_str_mv 2009-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/82059
Ceballos, Laura; Elissondo, María Celina; Sanchez Bruni, Sergio Fabian; Denegri, Guillermo Maria; Alvarez, Luis Ignacio; et al.; Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice; Elsevier Ireland; Parasitology International; 58; 4; 12-2009; 354-358
1383-5769
CONICET Digital
CONICET
url http://hdl.handle.net/11336/82059
identifier_str_mv Ceballos, Laura; Elissondo, María Celina; Sanchez Bruni, Sergio Fabian; Denegri, Guillermo Maria; Alvarez, Luis Ignacio; et al.; Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice; Elsevier Ireland; Parasitology International; 58; 4; 12-2009; 354-358
1383-5769
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.parint.2009.07.006
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/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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 13.13397

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