Effect of ruminal microflora on the biotransformation of netobimin, albendazole, albendazole sulfoxide, and albendazole sulfoxide enantiomers in an artificial rumen

The effect of ruminai flora on the disposition of benzimidazole anthelmintic drugs was studied in dual-flow continuous-culture fermenters (artificial rumens). Six 1,320-mL artificial rumens were inoculated with ruminai fluid and fermentation conditions were maintained constant at 39°C, pH 6.4, solid dilution rate of 5%/h, and liquid dilution rate of 10%/h to simulate standard ruminai fermentation conditions. The study was repeated in two consecutive periods. Two hours after the inoculation of rumen fluid, the fermenters were fed 30 g of a 60:40 forage:concentrate ration. Within each period two fermenters per treatment were immediately dosed with 104 mg of netobimin, 52 mg of albendazole, or 39 mg of albendazole sulfoxide. Concentrations of netobimin, albendazole, albendazole sulfoxide and its enantiomers, and albendazole sulfone were analyzed by high performance liquid chromatography at 0.25, 0.5, 1, 2, 4, 6, and 8 h after dosage. Reductive metabolism by the ruminai bacteria was observed, favoring the production of albendazole, the most potent anthelmintic molecule. No differences in the production or consumption of albendazole sulfoxide enantiomers were observed, indicating that the ruminai bacteria metabolism was not enantioselective. Because benzimidazole anthelmintic drugs are generally administered orally, the ruminai flora play an important role in the bioavailability of these drugs. In our study, increased concentrations of albendazole in the three treatments, due to reductive ruminai biotransformation, suggests that ruminal biotransformation may improve the efficacy of orally administered netobimin, albendazole, and albendazole sulfoxide.