A study to assess the correlation between plasma, oral fluid and urine concentrations of flunixin meglumine with the tissue residue depletion profile in finishing-age swine

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2020-06-22
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Bates, Jessica
Karriker, Locke
Rajewski, Suzanne
Lin, Zhoumeng
Gehring, Ronette
Li, Mengjie
Riviere, Jim
Coetzee, Johann
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Karriker, Locke
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Veterinary Microbiology and Preventive Medicine
Our faculty promote the understanding of causes of infectious disease in animals and the mechanisms by which diseases develop at the organismal, cellular and molecular levels. Veterinary microbiology also includes research on the interaction of pathogenic and symbiotic microbes with their hosts and the host response to infection.
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Veterinary Diagnostic and Production Animal Medicine
The mission of VDPAM is to educate current and future food animal veterinarians, population medicine scientists and stakeholders by increasing our understanding of issues that impact the health, productivity and well-being of food and fiber producing animals; developing innovative solutions for animal health and food safety; and providing the highest quality, most comprehensive clinical practice and diagnostic services. Our department is made up of highly trained specialists who span a wide range of veterinary disciplines and species interests. We have faculty of all ranks with expertise in diagnostics, medicine, surgery, pathology, microbiology, epidemiology, public health, and production medicine. Most have earned certification from specialty boards. Dozens of additional scientists and laboratory technicians support the research and service components of our department.
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Abstract

Background

Flunixin meglumine (FM) was investigated for the effectiveness of plasma, oral fluid, and urine concentrations to predict tissue residue depletion profiles in finishing-age swine, along with the potential for untreated pigs to acquire tissue residues following commingled housing with FM-treated pigs. Twenty pigs were housed in groups of three treated and one untreated control. Treated pigs received one 2.2 mg/kg dose of FM intramuscularly. Before treatment and at 1, 3, 6, 12, 24, 36, and 48 h (h) after treatment, plasma samples were taken. At 1, 4, 8, 12 and 16 days (d) post-treatment, necropsy and collection of plasma, urine, oral fluid, muscle, liver, kidney, and injection site samples took place. Analysis of flunixin concentrations using liquid chromatography/tandem mass spectrometry was done. A published physiologically based pharmacokinetic (PBPK) model for flunixin in cattle was extrapolated to swine to simulate the measured data.

Results

Plasma concentrations of flunixin were the highest at 1 h post-treatment, ranging from 1534 to 7040 ng/mL, and were less than limit of quantification (LOQ) of 5 ng/mL in all samples on Day 4. Flunixin was detected in the liver and kidney only on Day 1, but was not found 4–16 d post-treatment. Flunixin was either not seen or found less than LOQ in the muscle, with the exception of one sample on Day 16 at a level close to LOQ. Flunixin was found in the urine of untreated pigs after commingled housing with FM-treated pigs. The PBPK model adequately correlated plasma, oral fluid and urine concentrations of flunixin with residue depletion profiles in liver, kidney, and muscle of finishing-age pigs, especially within 24 h after dosing.

Conclusions

Results indicate untreated pigs can be exposed to flunixin by shared housing with FM-treated pigs due to environmental contamination. Plasma and urine samples may serve as less invasive and more easily accessible biological matrices to predict tissue residue statuses of flunixin in pigs at earlier time points (≤24 h) by using a PBPK model.

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This article is published as Bates, Jessica L., Locke A. Karriker, Suzanne M. Rajewski, Zhoumeng Lin, Ronette Gehring, Mengjie Li, Jim E. Riviere, and Johann F. Coetzee. "A study to assess the correlation between plasma, oral fluid and urine concentrations of flunixin meglumine with the tissue residue depletion profile in finishing-age swine." BMC Veterinary Research 16, no. 1 (2020). DOI: 10.1186/s12917-020-02429-w. Posted with permission.

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Wed Jan 01 00:00:00 UTC 2020
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