ALVAREZ Luis Ignacio
Albendazole treatment in cystic echinococcosis: pharmacokinetics and clinical efficacy of two different aqueous formulations Ceballos, L.
CEBALLOS, L.; ELISSONDO, C.; MORENO, L.; SANCHEZ BRUNI, S.; DENEGRI, G.; ALVAREZ, L.; LANUSSE, C.
Año: 2008 vol. 103 p. 355 - 362
Abstract Albendazole (ABZ), a benzimidazole methylcarbamate compound, is approved for the treatment of the echinococcosis cystic disease in humans. The aim of the present work was to investigate the pharmacokinetic (PK) behaviour and clinical efficacy of two different ABZ formulations on hydatid cysts in infected mice. In the PK study, BalbC mice were orally treated with either, an aqueous solution or an aqueous suspension of ABZ (50 µg/mL). Plasma samples were collected between 0 and 16 h post-treatment and processed for ABZ/metabolites quantification. The efficacy study involved two different Experiments (1 and 2) where BalbC mice were artificially infected with Echinococcus granulosus protoscoleces (1500 protoescoleces/animal). Eight months post-infection the animals were allocated into three experimental groups: 1) Untreated control group, 2) ABZ-solution treated group and 3) ABZ- suspension treated group. Each treated group received ABZ (orally at 0.5 mg/kg) in two different treatment schemes: Experiment 1) every 48 h, during 30 days, Experiment 2) every 12 h, over 15 days. Mice were sacrificed after treatments and whole cysts were recovered and weighed. Transmission electron microscopy (TEM) was performed for cysts obtained from the different experimental groups. A higher ABZ-sulphoxide (ABZSO) systemic availability was observed in the animals treated with the ABZ aqueous solution compared to those treated with the suspension. The administration of ABZ over 30 days every 48 h did not result in statistical differences on the weight of the recovered cyst compared to untreated animals. However, both ABZ formulations were highly effectives in mice treated during 15 days every 12 h. The complementary information on ABZ kinetic disposition in infected mice and its clinical efficacy using different formulations and dosage regimens may contribute to identify improved chemical control for the hydatid disease. Keywords: Cystic echinococcosis, albendazole, pharmacokinetic, clinical efficacy