Flubendazole and albendazole capacity to accumulate into hydatid cysts in mice

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

Tandil, Buenos Aires

Congreso; XL Reunion Anual de la Sociedad Argentina de Farmacologia Experimental; 2008

SAFE

Few chemotherapeutic agents are available for the medical management of hydatid disease. The aim of this work was to evaluate the plasma pharmacokinetic (PK) behaviour of albendazole (ABZ) and flubendazole (FLBZ) and their ability to accumulate into hydatid cyst of infected mice. BalbC mice (n= 88) infected with E. granulosus (eight months of infection) were orally treated with a FLBZ or ABZ solution (5 mg/kg). Blood and cysts samples were collected between 0 and 12 h post-treatment and analysed for FLBZ-ABZ/metabolites by HPLC. FLBZ parent drug was detected in plasma (AUC=1.8 ± 0.16 ìg.h/mL) and cysts (AUC=0.35 ± 0.13 ìg.h/mL) collected from treated animals, conversely the ABZ parent drug do not was detected neither in plasma nor cysts of animals treated with ABZ solution, instead of that its metabolite albendazole sulphoxide was the main molecule detected either in plasma (AUC= 4.4 ± 0.42 ìg.h/mL) or cysts (AUC= 1.50 ± 0.14 ìg.h/mL). The excellent efficacy observed for FLBZ (murine model) may be related with its ability to reach the cyst. In contrast after ABZ administration, the effect agains hydatid cyst depend on ABZSO, a metabolite with lower anthelmintic potency and reduced capacity to diffused trough the cysts wall.