Effect of ruminal microflora on the biotransformation of netobimin, albendazole, albendazole sulfoxide, and albendazole sulfoxide enantiomers in an artificial rumen.
The effect of ruminal 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 ruminal fluid and fermentation conditions were maintained constant at 39 degrees C, pH 6.4, solid dilution rate of 5%/h, and liquid dilution rate of 10%/h to simulate standard ruminal 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 ruminal 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 ruminal bacteria metabolism was not enantioselective. Because benzimidazole anthelmintic drugs are generally administered orally, the ruminal 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 ruminal biotransformation, suggests that ruminal biotransformation may improve the efficacy of orally administered netobimin, albendazole, and albendazole sulfoxide.
Capece
B P
BP
Department of Pharmacology and Therapeutics, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Calsamiglia
S
S
Castells
G
G
Arboix
M
M
Cristòfol
C
C
D015766:Albendazole / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D000871:Anthelmintics / Q000378:metabolism*; D001711:Biotransformation; D002417:Cattle; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D005285:Fermentation; D006146:Guanidines / Q000378:metabolism*; D066298:In Vitro Techniques; D008956:Models, Chemical; D012417:Rumen / Q000382:microbiology*; D013237:Stereoisomerism
D000871:Anthelmintics; D006146:Guanidines; D015766:Albendazole; C027186:albendazole sulfoxide; C049626:netobimin