Plasma, Urine and Tissue Concentrations of Flunixin and Meloxicam in Pigs

Abstract

Background: The objective of this study was to compare plasma and urine concentrations of flunixin and meloxicam in pigs, in order to determine urine withdrawal intervals for animals at livestock shows where urine is routinely tested for these drugs. Fourteen Yorkshire/Landrace cross pigs were housed in individual metabolism cages to facilitate complete urine collection. All animals were randomly divided into one of two treatment groups and received either 2.2 mg/kg flunixin or 0.4 mg/kg meloxicam via intramuscular injection. Plasma and urine were collected and analyzed by UPLC-MS/MS. Pigs were humanely euthanized when meloxicam/flunixin could no longer be detected in two consecutive urine samples, and liver and kidneys were collected to quantify any potential residues.Results: Drug levels in urine reached peak concentrations between 4 and 8 h post-dose for both flunixin and meloxicam. Flunixin urine concentrations were higher than maximum levels determined in plasma. Urine concentrations for flunixin and meloxicam were last detected above the limit of quantification (LOQ) at 120 h (0.0005 μg/mL) and 48 h (0.001 μg/mL), respectively. Mean apparent elimination half-life in plasma was 5.00 ± 1.89 h and 3.22 ± 1.52 h for flunixin and meloxicam, respectively. Six of seven pigs had detectable liver concentrations of flunixin (range 0.0001-0.0012 μg/g) following negative urine samples at 96 and 168 h, however all samples at 168 h were below the FDA tolerance level (0.03 μg/g). Meloxicam was detected in a single liver sample at necropsy (0.0054 μg/g) at 72 h but was below the EU MRL (0.065 μg/g) which was used to determine a safety level when FDA tolerance or FSIS testing limits were not established. Urine concentrations did not relate to liver residues at the single slaughter time Conclusions: This data suggests that pigs given a single intramuscular dose of meloxicam at 0.4 mg/kg or flunixin at 2.2 mg/kg are unlikely to have tissue residues above the US FDA tolerance or EU MRL following negative urine testing. This information will assist in generating withdrawal intervals for these NSAIDs for show pigs that might undergo a urine test by the livestock show authorities.

Pharmacokinetic of Flunixin Meglumine in Broiler Chicks by Enzyme-linked Immunosorbent Assay

“…Also, the rate of drug excretion which has a highly binding to protein is weak, the reason is that the glomerular filtration in the kidneys and hepatic metabolism are limited only to the free molecule of drug in the plasma [21]. Flunixin is a fat-soluble drug that spreads widely in the body, and it has been shown binds strongly to plasma proteins [22].…”