The need to identify improved
therapy against
cystic echinococcosis (CE) has motivated pharmacology-based research. The comparative pharmacological performances of the
benzimidazole compounds
flubendazole (FLBZ) and
albendazole (ABZ) were addressed here. The goals of the work were as follows: (i) to evaluate the ex vivo activities of FLBZ, ABZ, and their respective metabolites against Echinococcus granulosus protoscoleces, (ii) to compare the plasma and
cyst disposition kinetics for the two drugs in infected mice, and (iii) to compare the clinical efficacies of FLBZ and ABZ against CE in mice. For the ex vivo study, E. granulosus protoscoleces were incubated with FLBZ, reduced FLBZ (R-FLBZ), ABZ, and ABZ-
sulfoxide (ABZSO) (10 nmol/ml). Protoscolex viability was monitored by the
methylene blue exclusion test and scanning electron microscopy (SEM). For the pharmacokinetic study, BALB/c mice with CE were allocated to two different groups and orally treated with either FLBZ or ABZ (5 mg/kg of
body weight), both formulated as a
cyclodextrin-based
solution. Blood and
cyst samples were taken up to 12 h posttreatment and analyzed by high-performance liquid chromatography (HPLC). For the efficacy study, CE-infected BALB/c mice were divided into three groups: the unmedicated control group and the FLBZ- and ABZ-treated groups. Oral treatments were performed twice a day during 25 days.
After treatment, all animals were killed and the weight of the
cysts was recorded. Loss of protoscolex viability was observed after
drug incubation. FLBZ was detected in plasma (area under the concentration-versus-time curve [AUC] = 1.8 μg · h/ml) and
cysts (AUC = 0.3 μg · h/g) collected from treated infected animals. Conversely, ABZSO was the only active molecule measured in plasma (AUC = 4.4 μg·h/ml) and
cysts (AUC = 1.5 μg·h/g) after ABZ treatment. FLBZ induced a 90% reduction in
cyst weight in comparison to those collected from untreated control mice (P < 0.05). However, no differences in
cyst weight were observed between the ABZ-treated (8.2 g) and unmedicated control (10.5 g) groups. Due to these results, we consider
flubendazole to have great potential to become a
drug of choice in the treatment of
cystic echinococcosis.