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dc.contributor.author
Ceballos, Laura  
dc.contributor.author
Mackenzie, Charles  
dc.contributor.author
Geary, Timothy  
dc.contributor.author
Alvarez, Luis Ignacio  
dc.contributor.author
Lanusse, Carlos Edmundo  
dc.date.available
2017-11-10T20:02:04Z  
dc.date.issued
2014-05  
dc.identifier.citation
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  
dc.identifier.uri
http://hdl.handle.net/11336/27942  
dc.description.abstract
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.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Public Library Of Science  
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
Filariasis  
dc.subject
Cyclodextrins  
dc.subject.classification
Otras Ciencias Veterinarias  
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Ciencias Veterinarias  
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CIENCIAS AGRÍCOLAS  
dc.title
Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2016-11-17T16:04:02Z  
dc.identifier.eissn
1935-2735  
dc.journal.volume
8  
dc.journal.number
5  
dc.journal.pagination
2838-2844  
dc.journal.pais
Estados Unidos  
dc.journal.ciudad
San Francisco  
dc.description.fil
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  
dc.description.fil
Fil: Mackenzie, Charles. Michigan State University; Estados Unidos  
dc.description.fil
Fil: Geary, Timothy. McGill University; Canadá  
dc.description.fil
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  
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.journal.title
Neglected Tropical Diseases  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pntd.0002838  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038472/  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://doaj.org/article/895854c466d345af95aa7eb66cb075a2  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002838