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Excretory, Secretory, and Tissue Residues after Label and Extra-label Administration of Flunixin Meglumine to Saline- or Lipopolysaccharide-Exposed Dairy Cows

David J. Smith, Weilin L. Shelver, Ronald E. Baynes, Lisa Tell, Ronette Gehring, Mingjie Li, Terry Dutko, J. W. Schroeder, Grant Herges, Jim E. Riviere
Journal of Agricultural and Food Chemistry 2015 v.63 no.19 pp. 4893-4901
animal tissues, dairy cows, drug residues, flunixin, intramuscular injection, intravenous injection, lactation, lipopolysaccharides, liver, milk, pharmacokinetics, urine
Twenty lactating dairy cattle were intravenously infused with either lipopolysaccharide (LPS) (n = 10) or sterile saline (n = 10). Five cattle in each group received three doses of flunixin meglumine administered by either intravenous infusion or intramuscular injection at 24 h intervals. Milk, urine, and tissues were collected. Thirty-six hours after the last flunixin administration, milk from six cows contained 5-hydroxyflunixin (5OHF) levels greater than the milk tolerance of 2 ng/mL; by 48 h, milk from two cows, a saline and a LPS-treated animal, had violative milk concentrations of 5OHF. A single animal treated with LPS and intramuscular flunixin contained violative flunixin residues in liver. The ratio of urinary flunixin/5OHF was correlated (P < 0.01; R2 = 0.946) with liver flunixin residues in LPS-treated animals, but not (P = 0.96; R2 = 0.003) in cows treated with saline in lieu of LPS. Violative residues of flunixin in dairy cattle may be related to LPS inhibition of flunixin metabolism.