title: Bioconversion of netobimin pro-drug by gastrointestinal fluids of ruminants.
abstract: The biotransformation of netobimin (NTB) pro-drug by ruminal, abomasal and intestinal fluids of sheep and cattle was investigated under anaerobic conditions in vitro. No metabolic conversion of NTB was observed upon incubation with abomasal fluid or boiled samples of different gastrointestinal fluids. NTB pro-drug was reduced and cyclised into albendazole (ABZ) and this further oxidized into ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO2) by both sheep and cattle ruminal and ileal fluids. A zwitterion formulation of NTB produced a significantly greater amount of anthelminthically active ABZ metabolites (ABZ and ABZSO) than a trisamine salt formulation of the same compound. Although there was no difference in the total amount of products formed, both cattle ruminal and ileal fluids showed a greater oxidative capacity than sheep derived fluids. This was evidenced by the greater amounts of ABZSO recovered and by the resultant lower ratios of ABZ/ABZSO obtained with cattle fluids.
authors.affiliation: Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Québec, Canada.
authors.forename: C E
authors.initials: CE
authors.lastname: Lanusse
authors.forename: B
authors.initials: B
authors.lastname: Nare
authors.forename: L H
authors.initials: LH
authors.lastname: Gascon
authors.forename: R K
authors.initials: RK
authors.lastname: Prichard
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics*; D001711:Biotransformation; D002417:Cattle; D004064:Digestive System / Q000378:metabolism*; D006146:Guanidines / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000493:pharmacokinetics*; D012418:Ruminants / Q000378:metabolism*; D012756:Sheep
chemical_list: D000871:Anthelmintics; D006146:Guanidines; D011355:Prodrugs; C049626:netobimin