Flubendazole in cystic echinococosis therapy: Pharmaco-Parasitological evaluation in mice

CEBALLOS, , L.;; ELISONDO , C,; SANCHEZ BRUNI SF; DENEGRI, G.; ALVAREZ, L.;; LANUSSE, C.,

PARASITOLOGY INTERNATIONAL

ELSEVIER IRELAND LTD

Año: 2010 vol. 56 p. 386 - 392

1383-5769

Cystic echinococcosis (CE) caused by the parasite Echinococcus granulosus is an important public healthproblem 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 workwere: a) to compare the plasma pharmacokinetic behaviour of flubendazole formulated as a hydroxipropyl-â-cyclodextrin aqueous solution or as a carboxymethyl celullose suspension, both given by the oral route tomice, b) to compare flubendazole clinical efficacy in secondary CE in mice after its administration as bothformulations, c) to evaluate the flubendazole-induced morphological changes in hydatid cysts recoveredfrom infected mice treated with both drug formulations. Flubendazole administration as a solution resultedin 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 drugavailability correlated with an increased efficacy against secondary CE in mice observed for the flubendazolesolutionformulation, while the suspension formulation did not reach differences with the untreated controlgroup. Similar ultrastructural changes were observed in cysts recovered from flubendazole (bothformulations) treated mice after 3, 6 and 9 months of infection, although the damage extension was greaterafter treatment with the flubendazole-solution formulation.© 2009 Elsevier Ireland Ltd. All rights reserved.