Comparative plasma and urine concentrations of flunixin and meloxicam in goats

Bublitz, Claire M.; Mzyk, Danielle A.; Mays, Travis; Fajt, Virginia R.; Hairgrove, Thomas; Baynes, Ronald E.

doi:10.1016/j.smallrumres.2019.01.013

Cited by 12 publications

(21 citation statements)

References 18 publications

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“…The relationship between plasma and urine flunixin concentrations across all time points indicates that urine flunixin concentrations were higher than those measured in plasma at any given time point, similar to previously reported in both cattle and goats (2,6), however this was the opposite for meloxicam, with plasma concentrations being similar to or higher than that of the urine, again, similar to previously reported in goats (2). Glomerular filtration rate of 7-week-old pigs has been reported at 4.31 mL/min/kg (258.6 mL/h/kg; (27)), which is greater than the renal clearance values for both meloxicam and flunixin in this study, indicating that clearance of these NSAIDs is mainly via glomerular filtration with tubular reabsorption.…”

Section: Urine Pharmacokinetics and Renal Clearancesupporting

confidence: 89%

“…However, urine concentrations of drugs correlate in an unknown manner with plasma or tissue concentrations, particularly for drugs for which renal clearance is only a minor portion of the total clearance. Therefore, using urine concentrations to assess potential tissue residues could lead to inaccurate predictions of target tissue concentrations (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…Limited data are available regarding the relationship between urinary excretion of a drug and the plasma or tissue concentrations. Urine concentrations of flunixin have previously been examined in cattle, goats, horses, camels and dogs (2,3,(6)(7)(8)(9), as well as pigs (10,11). Of the two studies that examined flunixin in urine of pigs, only one of those attempted to establish a correlation with tissue concentrations.…”

Section: Introductionmentioning

confidence: 99%

“…However this study did not assess tissue concentrations of flunixin in pigs. 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 correlation between meloxicam concentrations in plasma, tissues and urine in pigs.…”

Section: Introductionmentioning

confidence: 99%

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

Nixon

Mays

Routh

et al. 2020

Preprint

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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.

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Section: Urine Pharmacokinetics and Renal Clearancesupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Nixon

Mays

Routh

et al. 2020

Preprint

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“…There are numerous studies describing unixin plasma and urine concentrations in cattle, goats, horses, camels and dogs (2,3,(6)(7)(8)(9), as well as pigs (10,11). It should also be noted that relationship between plasma and urine has been the background for doping control in horses (8,12).…”

Section: Introductionmentioning

confidence: 99%

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

Nixon

Mays

Routh

et al. 2020

Preprint

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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 of these drugs. 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 into 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.

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Electrospray ionization rapid screening sans liquid chromatography column: A sensitive method for detection and quantification of chemicals in animal tissues and urine

Chakrabarty

Shelver

Smith

2020

Rapid Comm Mass Spectrometry

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Rationale Electrospray ionization mass spectrometry (ESI‐MS) in conjunction with liquid chromatography (LC) can provide accurate quantitative data, but it is not well‐suited for the rapid screening (RS) of analytes incurred into complex matrices. This study was designed to determine the usefulness of ESI for rapid detection and quantitation of veterinary drugs from complex biological matrices under near real‐time conditions. Methods Nine veterinary drugs or metabolites, clenbuterol, erythromycin, flunixin, 5‐hydroxyflunixin, meloxicam, ractopamine, salbutamol, tylosin and zilpaterol, present in cow urine, sheep urine, sheep tissues (kidney, muscle, liver and lung) or pig kidney, were simultaneously analyzed. A simple sample clean‐up procedure, which included dilution with 10% sodium carbonate followed by extraction with ethyl acetate, was used. For tissues, an additional pre‐extraction with hexane was performed to remove fat prior to MS analysis. Samples were introduced into the mass spectrometer through the LC autosampler, but no chromatographic separation was employed. A Sciex 5600+ triple time‐of‐flight mass spectrometer with a dual‐spray source interfaced with a Shimadzu Nexera LC system was used. Samples were analyzed in positive ion mode. Results Sample extraction times were typically 10–30 min or less and instrumental analysis time was 1 min/sample. Regression coefficients of matrix‐matched standard curves across all compounds ranged from 0.9701–0.9999 in urine (cow and sheep) and tissues (sheep kidney, liver, lung, muscle and pig kidney). Limits of detection ranged from 0.11 to 2.03 ng/mL across analytes in urine and 0.11 to 8.86 ng/g across tissues. Correlations between RS‐ESI‐MS and LC/MS/MS results were 0.956 to 0.998 for incurred residues of flunixin in cow urine, ractopamine in pig kidney and zilpaterol in sheep urine. Conclusions RS‐ESI‐MS provided rapid, sensitive, and accurate analyses of nine veterinary drugs from complex matrices with very little sample preparation and produced quantitative data akin to LC/MS/MS.

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Comparative plasma and urine concentrations of flunixin and meloxicam in goats

Cited by 12 publications

References 18 publications

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

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

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

Electrospray ionization rapid screening sans liquid chromatography column: A sensitive method for detection and quantification of chemicals in animal tissues and urine

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