ABSTRACT
Albendazole (ABZ) is a methylcarbamate benzimidazole anthelmintic used to control gastrointestinal parasites in several animal species and humans. The type of diet has been identified as a major determinant for ABZ pharmacokinetics in different animal species and humans. The work described here assesses the pattern of the absorption and the systemic availability of ABZ and its metabolites after its oral administration to pigs under different feed management plans. Eighteen pigs (5 months old, local ecotype breeds) were distributed into three experimental groups. In the fasting group, the animals fasted for 8 h prior to treatment. In the pellet + oil and pellet groups, the animals were fed ad libitum with a commercial pelleted-based diet with or without the addition of soya oil. An ABZ suspension was orally administered at 10 mg/kg. Blood samples were taken over the 48 h post-treatment. The plasma samples were analyzed by HPLC. Under the described experimental conditions, the ingestion of the pellet-based diet with or without the soya oil before ABZ treatment did not significantly (p < 0.05) modify the plasma disposition kinetics of the ABZ sulfoxide (ABZSO, the main ABZ metabolite) compared to that observed in the fasting pigs. Both ABZ metabolites (ABZSO and ABZ sulphone) reached similar peak concentrations and systemic exposures in all the experimental groups regardless of the feeding management. However, the addition of oil to the pelleted food enhanced the pattern of ABZ absorption, which was reflected in the higher (p < 0.05) concentration profiles of the active ABZSO metabolite measured between 12 and 48 h post-treatment compared to the pigs fed with the pelleted food alone. Although this effect may not be therapeutically relevant after ABZ administration as a single oral dose, the overall impact of the type and feeding conditions when ABZ is supplemented with food for several days should be cautiously evaluated.
ABSTRACT
BACKGROUND: Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic compound. The parent FLBZ is metabolized to its reduced (R-FLBZ) and hydrolyzed (H-FLBZ) metabolites. There are no data on the potential nematodicidal activity of R-FLBZ, the main plasma metabolite found in sheep and mice. The goal of the current work was to assess the efficacy of FLBZ and R-FLBZ against Trichinella spiralis in a mouse model. METHODS: Both compounds were administered to Balb/c mice infected with T. spiralis as either a cyclodextrin aqueous solution or as a carboxymethylcellulose suspension. Treatments were performed orally (5 mg/kg) at 1 day after infection with T. spiralis. The efficacy of the treatments was assessed at day 6 after infection. RESULTS: While the efficacy obtained for FLBZ and R-FLBZ administered as a solution was 94 and 98%, respectively, the efficacies obtained after the treatment with FLBZ suspensions were 38% (FLBZ) and 64% (R-FLBZ). CONCLUSION: Under the current experimental conditions, a high nematodicidal efficacy of both FLBZ and R-FLBZ administered as solution preparations was observed.
