The objectives of the present study were, first, to establish a methodology for evaluation of the permeability in vitro of hydatid cysts to different drugs and, second, to compare the permeability to albendazole sulfoxide of cysts from untreated animals, cysts from animals treated with 50 mg/kg netobimin for 5 days, and cysts from animals treated with 50 mg/kg netobimin plus 1.1 mg/kg fenbendazole for 5 days. The drug flow follows the Fick law, i.e., the uptake occurs by simple diffusion. We calculated the permeability constant of the cyst membrane by taking into account the disappearance velocity constant, the cyst area, and the incubation solution volume. The permeability value obtained for albendazole sulfoxide was 8.06+/-2.30 x 10(-6) cm s(-1) in cysts from untreated animals, 5.56+/-2.53 x l0(-6) cm s(-1) in cysts from animals treated with netobimin, and 7.05+/-3.04 x 10(-6) cm s(-1) in cysts from animals treated with netobimin +/- fenbendazole. These permeability values show significant differences (P < 0.05).

The effect of netobimin and netobimin plus fenbendazole administration on secondary hydatid disease was studied. Secondary hydatid disease in gerbils (Meriones unguiculatus) was produced by intraperitoneal inoculation of protoscolices of Echinococcus granulosus. The experimental animals received doses of 20 and 50 mg/kg of netobimin or a mixture of netobimin and 1.7 mg/kg of fenbendazole. The results showed that after a single dose of netobimin at the studied concentrations, the cystic material transplanted into the mouse produced a significant recurrence of the disease, but the most remarkable finding was that the hydatid-cyst recurrence never took place when netobimin was given together with fenbendazole.

A comparison of the pharmacokinetic profiles of netobimin (NTB), albendazole sulfoxide (ABZSO) and albendazole sulfone (ABZSO2) was performed in gerbils (Meriones unguiculatus) with intra-abdominal hydatidosis and in healthy gerbils. The infection was developed after peritoneal inoculation of protoscolices of Echinooccus granulosus from sheep. Plasma concentrations of NTB, ABZSO and ABZSO2 were measured by HPLC after oral administration of 50 mg NTB kg(-1). The results showed an incomplete biotransformation of NTB over the experimental time; and this increased in infected animals. ABZSO and ABZSO2 pharmacokinetic profiles were unaffected and were similar in both non-infected and infected animals. Both hepatic and intestinal microsomal sulfoxidase activities were measured. Since infected gerbils induced hepatic activity and decreased intestinal activity, the total activity was not different in infected and non-infected animals. In summary, intra-abdominal hydatid disease affected the pharmacokinetic profile of NTB, but ABZSO and ABZSO2 plasma concentrations were not different in infected and non-infected gerbils.

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