INVESTIGADORES
LANUSSE Carlos Edmundo
artículos
Título:
Exploring the Potential of Flubendazole in Filariasis Control: Evaluation of the Systemic Exposure for Different Pharmaceutical Preparations
Autor/es:
CEBALLOS, L; MACKENZIE, C; GEARY, A; ALVAREZ, L; LANUSSE, C
Revista:
PLOS NEGLECTED TROPICAL DISEASES
Editorial:
PUBLIC LIBRARY SCIENCE
Referencias:
Lugar: San Francisco; Año: 2014
ISSN:
1935-2735
Resumen:
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.