Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations

Autores
Ceballos, Laura; Mackenzie, Charles; Geary, Timothy; Alvarez, Luis Ignacio; Lanusse, Carlos Edmundo
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The goal of elimination of the human filariases would benefit greatly from the use of a macrofilaricidal agent. In vivo trials in humans and many experimental animal models suggest that flubendazole (FLBZ) is a highly efficacious macrofilaricide. However, since serious injection site reactions were reported in humans after parenteral FLBZ administration, the search for alternative pharmaceutical strategies to improve the systemic availability of FLBZ and its metabolites has acquired urgency in both human and veterinary medicine. The goal of the current work was to compare the systemic exposure of FLBZ formulated as either an aqueous hydroxypropyl-b-cyclodextrin (CD) or aqueous carboxymethyl cellulose (CMC) suspension or a Tween 80-based formulation (TWEEN) in rats and jirds (Meriones unguiculatus). Healthy animals of both species were allocated into four experimental groups of 44 animals each: FLBZ-CDoral and FLBZ-CDsc, treated with the FLBZ-CD formulation by the oral or subcutaneous routes, respectively; FLBZ-TWEENsc, dosed subcutaneously with the FLBZ-TWEEN formulation; and FLBZ-CMCoral, treated orally with the FLBZ suspension. The FLBZ dose was 5 mg/kg. FLBZ and its hydrolyzed (H-FLBZ) and reduced (R-FLBZ) metabolites were recovered in plasma samples collected from rats and jirds treated with the different FLBZ formulations. In both species, FLBZ parent drug was the main analyte recovered in the bloodstream. In rats, FLBZ systemic exposure (AUC0-LOQ) was significantly (P,0.05) higher after the FLBZ-CD treatments, both oral (4.860.9 mg.h/mL) and subcutaneous (7.360.6 mg.h/mL), compared to that observed after oral administration of FLBZ-CMC suspension (0.9360.2 mg.h/mL). The same differences were observed in jirds. In both species, parenteral administration of FLBZ-TWEEN did not improve the systemic availability of FLBZ compared to FLBZ-CDoral treatment. In conclusion, formulation approaches that enhance the availability of flubendazole in the rat and jird may have therapeutic implications for a drug with poor or erratic bioavailability.
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: Mackenzie, Charles. Michigan State University; Estados Unidos
Fil: Geary, Timothy. McGill University; Canadá
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
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
Materia
FLUBENDAZOLE
FILARIASIS
CYCLODEXTRINS
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:11336/27942
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparationsCeballos, LauraMackenzie, CharlesGeary, TimothyAlvarez, Luis IgnacioLanusse, Carlos EdmundoFLUBENDAZOLEFILARIASISCYCLODEXTRINShttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4The goal of elimination of the human filariases would benefit greatly from the use of a macrofilaricidal agent. In vivo trials in humans and many experimental animal models suggest that flubendazole (FLBZ) is a highly efficacious macrofilaricide. However, since serious injection site reactions were reported in humans after parenteral FLBZ administration, the search for alternative pharmaceutical strategies to improve the systemic availability of FLBZ and its metabolites has acquired urgency in both human and veterinary medicine. The goal of the current work was to compare the systemic exposure of FLBZ formulated as either an aqueous hydroxypropyl-b-cyclodextrin (CD) or aqueous carboxymethyl cellulose (CMC) suspension or a Tween 80-based formulation (TWEEN) in rats and jirds (Meriones unguiculatus). Healthy animals of both species were allocated into four experimental groups of 44 animals each: FLBZ-CDoral and FLBZ-CDsc, treated with the FLBZ-CD formulation by the oral or subcutaneous routes, respectively; FLBZ-TWEENsc, dosed subcutaneously with the FLBZ-TWEEN formulation; and FLBZ-CMCoral, treated orally with the FLBZ suspension. The FLBZ dose was 5 mg/kg. FLBZ and its hydrolyzed (H-FLBZ) and reduced (R-FLBZ) metabolites were recovered in plasma samples collected from rats and jirds treated with the different FLBZ formulations. In both species, FLBZ parent drug was the main analyte recovered in the bloodstream. In rats, FLBZ systemic exposure (AUC0-LOQ) was significantly (P,0.05) higher after the FLBZ-CD treatments, both oral (4.860.9 mg.h/mL) and subcutaneous (7.360.6 mg.h/mL), compared to that observed after oral administration of FLBZ-CMC suspension (0.9360.2 mg.h/mL). The same differences were observed in jirds. In both species, parenteral administration of FLBZ-TWEEN did not improve the systemic availability of FLBZ compared to FLBZ-CDoral treatment. In conclusion, formulation approaches that enhance the availability of flubendazole in the rat and jird may have therapeutic implications for a drug with poor or erratic bioavailability.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: Mackenzie, Charles. Michigan State University; Estados UnidosFil: Geary, Timothy. McGill University; CanadáFil: 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; ArgentinaFil: 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; ArgentinaPublic Library Of Science2014-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/27942Ceballos, Laura; Mackenzie, Charles; Geary, Timothy; Alvarez, Luis Ignacio; Lanusse, Carlos Edmundo; Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations; Public Library Of Science; Neglected Tropical Diseases; 8; 5; 5-2014; 2838-28441935-2735CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pntd.0002838info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038472/info:eu-repo/semantics/altIdentifier/url/https://doaj.org/article/895854c466d345af95aa7eb66cb075a2info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002838info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:35Zoai:ri.conicet.gov.ar:11336/27942instacron: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 09:45:35.452CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations
title Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations
spellingShingle Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations
Ceballos, Laura
FLUBENDAZOLE
FILARIASIS
CYCLODEXTRINS
title_short Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations
title_full Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations
title_fullStr Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations
title_full_unstemmed Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations
title_sort Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations
dc.creator.none.fl_str_mv Ceballos, Laura
Mackenzie, Charles
Geary, Timothy
Alvarez, Luis Ignacio
Lanusse, Carlos Edmundo
author Ceballos, Laura
author_facet Ceballos, Laura
Mackenzie, Charles
Geary, Timothy
Alvarez, Luis Ignacio
Lanusse, Carlos Edmundo
author_role author
author2 Mackenzie, Charles
Geary, Timothy
Alvarez, Luis Ignacio
Lanusse, Carlos Edmundo
author2_role author
author
author
author
dc.subject.none.fl_str_mv FLUBENDAZOLE
FILARIASIS
CYCLODEXTRINS
topic FLUBENDAZOLE
FILARIASIS
CYCLODEXTRINS
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 goal of elimination of the human filariases would benefit greatly from the use of a macrofilaricidal agent. In vivo trials in humans and many experimental animal models suggest that flubendazole (FLBZ) is a highly efficacious macrofilaricide. However, since serious injection site reactions were reported in humans after parenteral FLBZ administration, the search for alternative pharmaceutical strategies to improve the systemic availability of FLBZ and its metabolites has acquired urgency in both human and veterinary medicine. The goal of the current work was to compare the systemic exposure of FLBZ formulated as either an aqueous hydroxypropyl-b-cyclodextrin (CD) or aqueous carboxymethyl cellulose (CMC) suspension or a Tween 80-based formulation (TWEEN) in rats and jirds (Meriones unguiculatus). Healthy animals of both species were allocated into four experimental groups of 44 animals each: FLBZ-CDoral and FLBZ-CDsc, treated with the FLBZ-CD formulation by the oral or subcutaneous routes, respectively; FLBZ-TWEENsc, dosed subcutaneously with the FLBZ-TWEEN formulation; and FLBZ-CMCoral, treated orally with the FLBZ suspension. The FLBZ dose was 5 mg/kg. FLBZ and its hydrolyzed (H-FLBZ) and reduced (R-FLBZ) metabolites were recovered in plasma samples collected from rats and jirds treated with the different FLBZ formulations. In both species, FLBZ parent drug was the main analyte recovered in the bloodstream. In rats, FLBZ systemic exposure (AUC0-LOQ) was significantly (P,0.05) higher after the FLBZ-CD treatments, both oral (4.860.9 mg.h/mL) and subcutaneous (7.360.6 mg.h/mL), compared to that observed after oral administration of FLBZ-CMC suspension (0.9360.2 mg.h/mL). The same differences were observed in jirds. In both species, parenteral administration of FLBZ-TWEEN did not improve the systemic availability of FLBZ compared to FLBZ-CDoral treatment. In conclusion, formulation approaches that enhance the availability of flubendazole in the rat and jird may have therapeutic implications for a drug with poor or erratic bioavailability.
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: Mackenzie, Charles. Michigan State University; Estados Unidos
Fil: Geary, Timothy. McGill University; Canadá
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
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
description The goal of elimination of the human filariases would benefit greatly from the use of a macrofilaricidal agent. In vivo trials in humans and many experimental animal models suggest that flubendazole (FLBZ) is a highly efficacious macrofilaricide. However, since serious injection site reactions were reported in humans after parenteral FLBZ administration, the search for alternative pharmaceutical strategies to improve the systemic availability of FLBZ and its metabolites has acquired urgency in both human and veterinary medicine. The goal of the current work was to compare the systemic exposure of FLBZ formulated as either an aqueous hydroxypropyl-b-cyclodextrin (CD) or aqueous carboxymethyl cellulose (CMC) suspension or a Tween 80-based formulation (TWEEN) in rats and jirds (Meriones unguiculatus). Healthy animals of both species were allocated into four experimental groups of 44 animals each: FLBZ-CDoral and FLBZ-CDsc, treated with the FLBZ-CD formulation by the oral or subcutaneous routes, respectively; FLBZ-TWEENsc, dosed subcutaneously with the FLBZ-TWEEN formulation; and FLBZ-CMCoral, treated orally with the FLBZ suspension. The FLBZ dose was 5 mg/kg. FLBZ and its hydrolyzed (H-FLBZ) and reduced (R-FLBZ) metabolites were recovered in plasma samples collected from rats and jirds treated with the different FLBZ formulations. In both species, FLBZ parent drug was the main analyte recovered in the bloodstream. In rats, FLBZ systemic exposure (AUC0-LOQ) was significantly (P,0.05) higher after the FLBZ-CD treatments, both oral (4.860.9 mg.h/mL) and subcutaneous (7.360.6 mg.h/mL), compared to that observed after oral administration of FLBZ-CMC suspension (0.9360.2 mg.h/mL). The same differences were observed in jirds. In both species, parenteral administration of FLBZ-TWEEN did not improve the systemic availability of FLBZ compared to FLBZ-CDoral treatment. In conclusion, formulation approaches that enhance the availability of flubendazole in the rat and jird may have therapeutic implications for a drug with poor or erratic bioavailability.
publishDate 2014
dc.date.none.fl_str_mv 2014-05
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/11336/27942
Ceballos, Laura; Mackenzie, Charles; Geary, Timothy; Alvarez, Luis Ignacio; Lanusse, Carlos Edmundo; Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations; Public Library Of Science; Neglected Tropical Diseases; 8; 5; 5-2014; 2838-2844
1935-2735
CONICET Digital
CONICET
url http://hdl.handle.net/11336/27942
identifier_str_mv Ceballos, Laura; Mackenzie, Charles; Geary, Timothy; Alvarez, Luis Ignacio; Lanusse, Carlos Edmundo; Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations; Public Library Of Science; Neglected Tropical Diseases; 8; 5; 5-2014; 2838-2844
1935-2735
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pntd.0002838
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038472/
info:eu-repo/semantics/altIdentifier/url/https://doaj.org/article/895854c466d345af95aa7eb66cb075a2
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002838
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publisher.none.fl_str_mv Public Library Of Science
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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