Plasma, urine and tissue concentrations of Flunixin and Meloxicam in Pigs

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RESEARCH ARTICLE

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Plasma, urine and tissue concentrations of Flunixin and Meloxicam in Pigs Emma Nixon1, Travis P. Mays2, Patricia A. Routh1, James L. Yeatts1, Virginia R. Fajt3, Thomas Hairgrove4 and Ronald E. Baynes1*

Abstract Background: The objective of this study was to determine the renal clearance of flunixin and meloxicam in pigs and compare plasma and urine concentrations and tissue residues. Urine clearance is important for livestock show animals where urine is routinely tested for these drugs. Fourteen Yorkshire/Landrace cross pigs were housed in individual metabolism cages to facilitate urine collection. This is a unique feature of this study compared to other reports. Animals received either 2.2 mg/kg flunixin or 0.4 mg/kg meloxicam via intramuscular injection and samples analyzed by mass spectrometry. Pigs were euthanized when drugs were no longer detected in urine and liver and kidneys were collected to quantify 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 in plasma. Urine concentrations for flunixin and meloxicam were last detected above the limit of quantification at 120 h and 48 h, respectively. The renal clearance of flunixin and meloxicam was 4.72 ± 2.98 mL/h/kg and 0.16 ± 0.04 mL/h/kg, 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 (0.0054 µg/g) at 72 h but was below the EU MRL (0.065 µg/g). Conclusions: These data suggest that pigs given a single intramuscular dose of meloxicam at 0.4 mg/kg or flunixin at 2.2 mg/kg are likely to have detectable levels of the parent drug in urine up to 2 days and 5 days, respectively, after the first dose, but unlikely to have tissue residues above the US FDA tolerance or EU MRL following negative urine testing. This information will assist veterinarians in the therapeutic use of these drugs prior to livestock shows and also inform livestock show authorities involved in testing for these substances. Keywords: Pig, Flunixin, Meloxicam, Pharmacokinetics, NSAIDs, Residue, Urine, Show

Background Livestock show authorities drug test the urine in show animals in order to ensure fair competition. One of the groups of drugs of importance in this setting is nonsteroidal anti-inflammatory drugs (NSAIDs), which may be used to conceal an injury that would otherwise prevent a * Correspondence: [email protected] 1 Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 27607 Raleigh, NC, United States Full list of author information is available at the end of the article

show animal from competing. Sh