title: Serum, milk, and tissue monensin concentrations in cattle with adequate and potentially toxic dietary levels of monensin: pharmacokinetics and diagnostic interpretation.
abstract: Used in both beef cattle and dairy cows, monensin can provide many health benefits but can, when unintended overexposures occur, result in adverse effects. Information on serum and tissue concentrations following overexposure and/or overt toxicosis which may aid in diagnostics and clinical outcome is lacking. The aim of this study was to determine concentrations of monensin in biological specimens following oral exposure for 10 days to an approved dose (1 mg/kg) and a higher dose (5 mg/kg) of monensin given daily on a body weight basis to 10 dairy cows. No deaths were reported; cows receiving 5 mg/kg showed early signs of toxicosis including depression, decreased feed intake, and diarrhea after 4 days of exposure. Histopathological findings were minimal in most cows. Pharmacokinetic modeling of the detected serum concentrations for the 1 and 5 mg/kg dose groups determined the Cmax , Tmax, and t1/2λ to be 0.87 and 1.68 ng/mL, 2.0 and 1.0 h, and 1.76 and 2.32 days, respectively. Mixed regression models showed that the dose level and days since last dose were significantly associated with monensin concentrations in all four tissues, and with cardiac troponin levels. The high dose resulted in a significant elevation of monensin in tissues at approximately 4.7 times compared to the monensin concentrations in the tissues of animals from the low-dose group. The cTnI concentrations in the high-dose group were 2.1 times that of cTnI in the low-dose group. Thus, the ability to diagnose monensin overexposure and/or toxicosis will improve from knowledge of biological monensin concentrations from this study.
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.|California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: B
authors.identifier: http://orcid.org/0000-0001-6765-5085
authors.initials: B
authors.lastname: Puschner
authors.affiliation: California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Bautista
authors.affiliation: Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: McKemie
authors.affiliation: California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Gallego
authors.affiliation: California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: L W
authors.initials: LW
authors.lastname: Woods
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Moore
authors.affiliation: Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Knych
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002417:Cattle; D005260:Female; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008892:Milk / Q000737:chemistry*; D008985:Monensin / Q000009:adverse effects / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D018482:Muscle, Skeletal / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D019209:Troponin C / Q000097:blood
chemical_list: D019209:Troponin C; D008985:Monensin