title: Effect of the ionophore antibiotic monensin on the ruminal biotransformation of benzimidazole anthelmintics.
abstract: The benzimidazole (BZD) anthelmintics, netobimin (NTB) pro-drug and albendazole sulphoxide (ABZSO) are reduced to albendazole (ABZ) by ruminal microflora. The aim of the current work was to evaluate the influence of the ionophore monensin (MON) on the in vitro biotransformation of NTB and ABZSO by sheep ruminal fluid. Ruminal fluid, collected from Corriedale sheep, was preincubated (24 h) either without (control) or with known MON concentrations (0.5, 1.5 and 3.0 microg/mL) at 38 degrees C under a CO2 atmosphere. Afterwards, aliquots from both MON-pretreated and control ruminal fluid samples were incubated (30 and 60 min) with 2 microg/mL of either NTB or ABZSO. Incubated samples were chemically extracted and analysed by High Performance Liquid Chromatography to quantify the metabolites formed. The rate of ABZ production after 30 min of NTB incubation with control ruminal fluid was 0.023 microg/min. Conversely, the rates of ABZ formation were significantly (P<0.05) lower (0.009, 0.011 and 0.013 microg/min) when NTB was incubated with ruminal fluid pretreated with MON (at 0.5, 1.5 and 3.0 microg/mL, respectively). After both incubation periods, the reduction of ABZSO to ABZ was 22 to 70% lower when the ruminal fluid was preincubated with the different MON concentrations. The lower ABZ production observed in the presence of MON may result in a modified availability of this molecule in the gastrointestinal (GI) tract and hence, on its anthelmintic efficacy against GI nematodes.
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiopatología, Núcleo FISFARVET, Facultad de Ciencias Veterinarias, UNCPBA, Tandil 7000, Argentina. gvirkel@vet.unicen.edu.ar
authors.forename: G
authors.initials: G
authors.lastname: Virkel
authors.forename: A
authors.initials: A
authors.lastname: Lifschitz
authors.forename: J
authors.initials: J
authors.lastname: Sallovitz
authors.forename: G
authors.initials: G
authors.lastname: Inza
authors.forename: C
authors.initials: C
authors.lastname: Lanusse
mesh_terms: D015766:Albendazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics*; D001711:Biotransformation; D004347:Drug Interactions; D005260:Female; D006146:Guanidines / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology*; D008985:Monensin / Q000494:pharmacology*; D011355:Prodrugs / Q000493:pharmacokinetics*; D012417:Rumen / Q000378:metabolism*; D012756:Sheep / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D000871:Anthelmintics; D006146:Guanidines; D007476:Ionophores; D011355:Prodrugs; D008985:Monensin; D015766:Albendazole; C027186:albendazole sulfoxide; C049626:netobimin