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

Abstract

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; R(2) = 0.946) with liver flunixin residues in LPS-treated animals, but not (P = 0.96; R(2) = 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.

Human Food Safety Implications of Variation in Food Animal Drug Metabolism

“…Numerous studies have shown that disease alters the pharmacokinetics of various drugs2101531. The degree of pharmacokinetic changes depends on the severity of the disease.…”

Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows

“…administration, the C 0 was determined to be 11.9 μg/ml and the C max was 5.50 μg/ml after i.m. administration in adult Holsteins (Smith et al., ).…”

Transport of Potential Manure Hormone and Pharmaceutical Contaminants through Intact Soil Columns

“…In that study, flunixin was detected in the highest concentrations of eight compounds measured by gas chromatography–mass spectrometry (Barker, 2008). No studies report the presence or threat of flunixin from cattle manure despite that flunixin regularly exceeds residue levels in meat and milk of cattle (Leavens et al, 2014; Smith et al, 2015). Dairy cows accounted for 59% of flunixin violations in 2014 (USDA‐FSIS‐OPHS, 2015), with multiple studies finding that cattle are still excreting flunixin in their milk at concentrations above the regulatory limit after a 36‐h holding period (Kissell et al, 2013; Smith et al, 2015).…”

“…No studies report the presence or threat of flunixin from cattle manure despite that flunixin regularly exceeds residue levels in meat and milk of cattle (Leavens et al, 2014; Smith et al, 2015). Dairy cows accounted for 59% of flunixin violations in 2014 (USDA‐FSIS‐OPHS, 2015), with multiple studies finding that cattle are still excreting flunixin in their milk at concentrations above the regulatory limit after a 36‐h holding period (Kissell et al, 2013; Smith et al, 2015). Additionally, the metabolite 5‐hydroxyflunixin is excreted for longer periods of time than its parent molecule in milk (Smith et al, 2015).…”

“…Dairy cows accounted for 59% of flunixin violations in 2014 (USDA‐FSIS‐OPHS, 2015), with multiple studies finding that cattle are still excreting flunixin in their milk at concentrations above the regulatory limit after a 36‐h holding period (Kissell et al, 2013; Smith et al, 2015). Additionally, the metabolite 5‐hydroxyflunixin is excreted for longer periods of time than its parent molecule in milk (Smith et al, 2015). This metabolite was not measured in our studies, but it would be informative to know how the mobility and biochemical significance of 5‐hydroxyflunixin in soil compares with the parent molecule.…”