Flubendazole in cystic echinococcosis therapy: pharmaco-parasitological evaluation in mice

Abstract

Cystic echinococcosis (CE) caused by the parasite Echinococcus granulosus is an important public health problem worldwide. Flubendazole has shown poor in vivo efficacy against CE in humans and mice. However, flubendazole causes marked in vitro damage on E. granulosus protoscoleces. The goals of the current work were: a) to compare the plasma pharmacokinetic behaviour of flubendazole formulated as a hydroxipropyl-β-cyclodextrin aqueous solution or as a carboxymethyl celullose suspension, both given by the oral route to mice, b) to compare flubendazole clinical efficacy in secondary CE in mice after its administration as both formulations, c) to evaluate the flubendazole-induced morphological changes in hydatid cysts recovered from infected mice treated with both drug formulations. Flubendazole administration as a solution resulted in significantly higher plasma maximum concentration (Cmax) and area under the concentration-time curve (AUC) values compared to those obtained after the flubendazole-suspension treatment. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the flubendazole-solution formulation, while the suspension formulation did not reach differences with the untreated control group. Similar ultrastructural changes were observed in cysts recovered from flubendazole (both formulations) treated mice after 3, 6 and 9 months of infection, although the damage extension was greater after treatment with the flubendazole-solution formulation.