Comparison of pharmacokinetics and milk elimination of flunixin in healthy cows and cows with mastitis

Abstract

Pharmacokinetics and elimination of flunixin and 5-hydroxy flunixin in milk differed between mastitic and healthy cows, resulting in violative residues. This may partially explain the high number of flunixin residues reported in beef and dairy cattle. This study also raised questions as to whether healthy animals should be used when determining withdrawal times for meat and milk.

Comparative plasma and interstitial fluid pharmacokinetics of flunixin meglumine and ceftiofur hydrochloride following individual and co‐administration in dairy cows

“…Compared with the FLU PK parameters reported by Kissell et al. (), we found similar values for MRT but higher values for V area and CL. We also report substantially lower values for AUC.…”

“…We detected FLU in plasma samples up to 30 hr post‐treatment, 18 hr longer than reported by Kissell et al. (); however, we implemented lower LOD and LOQ levels. Mean FLU protein binding was determined to be 98.6% in both treatment groups, which is slightly lower than values reported by Anderson et al.…”

“…Kissell et al. () reported a mean peak plasma concentration of 18.35 μg/ml, which occurred 15 min following injection and not being able to find flunixin in plasma after 12 hr following treatment. Our initial plasma observed concentration ( C O ) was determined to be 22.62 ± 1.06 μg/ml and 20.52 ± 2.22 μg/ml for the FM and CF treatments, respectively.…”

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.…”

“…Subsequent studies are then conducted employing this fixed ratio in larger number of healthy animals to determine a withdrawal time after cessation of drug administration that will deplete target tissues to below the TOL or MRL for the marker residue. Due to these flaws, violative drug residues in the edible tissues of food-producing animals may occur when drugs are used in an extralabel manner or when disease is present even though the animals are slaughtered according to regulatory labeled withdrawal times23. Commonly reported drug violations include ceftiofur, enrofloxacin, flunixin, and sulfamethazine4.…”