Abstract
BackgroundThe 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.ResultsDrug 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).ConclusionsThese 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.
Highlights
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
Prior to this study there were data gaps pertaining to the renal clearance of this drug and how long it will take for the parent form of these drugs to clear from urine
While pharmacokinetics parameters from our study were comparable to earlier studies in pigs for these two drugs and a small percentage of the parent drug is cleared in the urine as demonstrated in other species, our study is the first to report the renal clearance of these two Nonsteroidal antiinflammatory drug (NSAID) in pigs
Summary
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. 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. That study used a single spot urine sample taken at necropsy to predict the residue depletion profile in edible tissues. The author recommended that future studies should consider using metabolism cages to collect cumulative urine samples to improve the prediction of tissue concentrations. This was a primary goal of our current study. There are far fewer data available regarding meloxicam concentration-time profiles in urine in large animal species, with only two studies in horses and goats [2, 13], and no published studies have assessed the relationship between meloxicam concentrations in plasma, tissues and urine in pigs
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