Flubendazole kinetic behaviour: ability to difusse into hydatid cysts in mice

CEBALLOS, L.; ELISSONDO, C.; ALVAREZ, L.; SÁNCHEZ BRUNI, S; DENEGRI, G.; LANUSSE, C.

Buenos Aires

Congreso; XXXIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2007

Sociedad Argentina de Farmacología Experimental

Flubendazole (FLBZ) has shown efficacy against protoscoleces of Echinococcus granulosus in vivo and in vitro. The aim of this work was to evaluate the plasma pharmacokinetic (PK) behaviour of FLBZ and its ability to access the hydatid cyst in infected mice. BalbC mice (n= 44) infected with E. granulosus (eight months of infection) were orally treated with a FLBZ-cyclodextrin solution (5 mg/kg). Blood and cysts samples were collected between 0 and 12 h post-treatment and analysed for FLBZ/metabolites by HPLC. FLBZ, the main analyte detected in plasma, reached a Cmax value of 1.55 µg/mL and was fast depleted from the bloodstream. A reduced-FLBZ metabolite was the main molecule recovered in plasma. While FLBZ peaked at 15 min post-administration in plasma, its higher cyst concentration (0.1 µg/g) was achieved at 52 min post-treatment. FLBZ concentrations within the cysts were significantly higher than those measured for its reduced and hydrolyzed metabolites. The higher lipophilicity of parent FLBZ may account for a greater diffusion rate through the cyst wall compared to that observed for its more polar metabolites.