Cover American Journal of Veterinary Research
American Journal of Veterinary Research
ISSN:
0002-9645
Publication Date:
01 Jun 2016

  • 1. FDA. Freedom of information summary: supplemental new animal drug application. NADA 101–479. Banamine injectable solution (flunixin meglumine). Available at: www.fda.gov/downloads/AnimalVeterinary/Products/ApprovedAnimalDrug-Products/FOIADrugSummaries/ucm064910.pdf. Accessed May 4, 2015.

  • 2. Fajt VR, Wagner SA, Norby B. Analgesic drug administration and attitudes about analgesia in cattle among bovine practitioners in the United States. J Am Vet Med Assoc 2011; 238: 755–767.

    • Search Google Scholar
    • Export Citation

  • 3. Sundlof SF, Kaneene JB, Miller RA. National survey on veterinarian-initiated drug use in lactating dairy cows. J Am Vet Med Assoc 1995; 207: 347–352.

    • Search Google Scholar
    • Export Citation

  • 4. Barnett SC, Sischo WM, Moore DA, et al. Evaluation of flunixin meglumine as an adjunct treatment for diarrhea in dairy calves. J Am Vet Med Assoc 2003; 223: 1329–1333.

    • Search Google Scholar
    • Export Citation

  • 5. USDA FSIS. Residue sample results-red books from 2005–2011. Available at: www.fsis.usda.gov/wps/portal/fsis/topics/data-collection-and-reports/chemistry/red-books/archive/. Accessed May 5, 2015.

  • 7. USDA FSIS. Residue repeat violator list for use by FSIS inspection program personnel part 1. Available at:www.fsis.usda.gov/wps/wcm/connect/f69f356d-0ae7-4007-b334-bca63c6703a0/Residue_IPP.pdf?MOD=AJPERES. Accessed Jul 30, 2014.

  • 8. Cera DA. Drug residues in animal derived foods. Available at: www.fda.gov/AnimalVeterinary/ScienceResearch/ucm248790.htm. Accessed May 6, 2015.

    • Search Google Scholar
    • Export Citation

  • 9. KuKanich B, Gehring R, Webb AI, et al. Effect of formulation and route of administration on tissue residues and withdrawal times. J Am Vet Med Assoc 2005; 227: 1574–1577.

    • Search Google Scholar
    • Export Citation

  • 10. Kissell LW, Leavens TL, Baynes RE, et al. Comparison of pharmacokinetics and milk elimination of flunixin in healthy cows and cows with mastitis. J Am Vet Med Assoc 2015; 246: 118–125.

    • Search Google Scholar
    • Export Citation

  • 11. Nouws JFM. Pharmacokinetics in immature animals: a review. J Anim Sci 1992; 70: 3627–3634.

  • 12. Boner PL, Liu DW, Feely WF, et al. Determination of flunixin in edible bovine tissues using liquid chromatography coupled with tandem mass spectrometry. J Agric Food Chem 2003; 51: 7555–7559.

    • Search Google Scholar
    • Export Citation

  • 13. Rivere J, ed. Comparative pharmacokinetics: principles, techniques and applications. 2nd ed. Ames, Iowa: Wiley-Blackwell, 2011;13–25.

    • Search Google Scholar
    • Export Citation

  • 14. Landoni MF, Cunningham FM, Lees P. Determination of pharmacokinetics and pharmacodynamics of flunixin in calves by use of pharmacokinetic/pharmacodynamic modeling. Am J Vet Res 1995; 56: 786–794.

    • Search Google Scholar
    • Export Citation

  • 15. Hardee GE, Smith JA, Harris SJ. Pharmacokinetics of flunixin meglumine in the cow. Res Vet Sci 1985; 39: 110–112.

  • 16. Odensvik K, Johansson IM. High-performance liquid chromatography method for determination of flunixin in bovine plasma and pharmacokinetics after single and repeated doses of the drug. Am J Vet Res 1995; 56: 489–495.

    • Search Google Scholar
    • Export Citation

  • 17. Shelver WL, Tell LA, Wagner SE, et al. Comparison of ELISA and LC-MS/MS for the measurement of flunixin plasma concentrations in beef cattle after intravenous and subcutaneous administration. J Agric Food Chem 2013; 61: 2679–2686.

    • Search Google Scholar
    • Export Citation

  • 18. Schwark WS. Factors that affect drug disposition in food-producing animals during maturation. J Anim Sci 1992; 70: 3635–3645.

  • 19. Anderson KL, Neff-Davis CA, Davis LE, et al. Pharmacokinetics of flunixin meglumine in lactating cattle after single and multiple intramuscular and intravenous administrations. Am J Vet Res 1990; 51: 1464–1467.

    • Search Google Scholar
    • Export Citation

  • 20. Odensvik K. Pharmacokinetics of flunixin and its effect on prostaglandin F2 alpha metabolite concentrations after oral and intravenous administration in heifers. J Vet Pharmacol Ther 1995; 18: 254–259.

    • Search Google Scholar
    • Export Citation

  • 21. Rantala M, Kaartinen L, Välimaki E, et al. Efficacy and pharmacokinetics of enrofloxacin and flunixin meglumine for treatment of cows with experimentally induced Escherichia coli mastitis. J Vet Pharmacol Ther 2002; 25: 251–258.

    • Search Google Scholar
    • Export Citation

  • 22. Jaroszewski J, Jedziniak P, Markiewicz W, et al. Pharmacokinetics of flunixin in mature heifers following multiple intravenous administration. Pol J Vet Sci 2008; 11: 199–203.

    • Search Google Scholar
    • Export Citation

  • 23. Kissell LW, Smith GW, Leavens TL, et al. Plasma pharmacokinetics and milk residues of flunixin and 5-hydroxy flunixin following different routes of administration in dairy cattle. J Dairy Sci 2012; 95: 7151–7157.

    • Search Google Scholar
    • Export Citation

  • 24. Lees P, May SA, White D. Pharmacokinetics and dosage regimens of anti-inflammatory drugs. Ann Rech Vet 1990; 21 (suppl 1):73S–78S.

    • Search Google Scholar
    • Export Citation

  • 25. Abo-El-Sooud K, Al-Anati L. Pharmacokinetic study of flunixin and its interaction with enrofloxacin after intramuscular administration in calves. Vet World 2011; 4: 449–454.

    • Search Google Scholar
    • Export Citation

  • 26. Fraccaro E, Coetzee JF, Odore R, et al. A study to compare circulating flunixin, meloxicam and gabapentin concentrations with prostaglandin E2 levels in calves undergoing dehorning. Res Vet Sci 2013; 95: 204–211.

    • Search Google Scholar
    • Export Citation

  • 27. Benitz AM. Pharmacology and pharmacokinetics of flunixin meglumine in the bovine, in Proceedings. 13th World Cong Diss Cattle 1984;928–930.

    • Search Google Scholar
    • Export Citation

  • 28. FDA. Freedom of information summary: supplemental new animal drug application. NADA 101–479. Banamine injectable solution (flunixin meglumine). Available at: www.fda.gov/downloads/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/FOIADrugSummaries/ucm064905.pdf. Accessed Feb 10, 2016.

  • 29. Banamine injectable solution [package insert]. Madison, NJ: Merck Animal Health, 2012.

  • 30. FDA. Guidance for industry: general principles for evaluating the safety of compounds used in food-producing animals. Available at: www.fda.gov/downloads/animalveterinary/guidancecomplianceenforcement/guidanceforindustry/ucm052180.pdf. Accessed May 5, 2015.

  • 31. USDA FSIS. Determination of flunixin in cattle liver by HPLC. Available at: www.fsis.usda.gov/wps/wcm/connect/9c74c267-8647-47a1-95ac-9241718432d2/clg-flx1.00.pdf?MOD=AJPERES. Accessed May 5, 2015.

Advertisement

Editorial Type:
Pharmacology

Pharmacokinetics and tissue elimination of flunixin in veal calves

Lindsey W. Kissell DVM, PhD1, Patrick D. Brinson DVM2, Ronette Gehring BVSc, MMED VET3, Lisa A. Tell DVM4, Scott E. Wetzlich BS5, Ronald E. Baynes DVM, PhD6, Jim E. Riviere DVM, PhD7, and Geof W. Smith DVM, PhD8
View More View Less
  • 1 Department of Population Health and Pathobiology, College of Veterinary Medicine, and Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC 27607.
  • | 2 Department of Population Health and Pathobiology, College of Veterinary Medicine, and Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC 27607.
  • | 3 Department of Anatomy and Physiology, College of Veterinary Medicine, and the Institute of Computational Comparative Medicine, Kansas State University, Manhattan, KS 66506.
  • | 4 Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 5 Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 6 Department of Population Health and Pathobiology, College of Veterinary Medicine, and Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC 27607.
  • | 7 Department of Anatomy and Physiology, College of Veterinary Medicine, and the Institute of Computational Comparative Medicine, Kansas State University, Manhattan, KS 66506.
  • | 8 Department of Population Health and Pathobiology, College of Veterinary Medicine, and Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC 27607.
DOI:
https://doi.org/10.2460/ajvr.77.6.634
Volume/Issue:
Volume 77: Issue 6
Online Publication Date:
01 Jun 2016
Restricted access
Reprints and Permissions Purchase Article

Abstract

OBJECTIVE To describe plasma pharmacokinetic parameters and tissue elimination of flunixin in veal calves.

ANIMALS 20 unweaned Holstein calves between 3 and 6 weeks old.

PROCEDURES Each calf received flunixin (2.2 mg/kg, IV, q 24 h) for 3 days. Blood samples were collected from all calves before the first dose and at predetermined times after the first and last doses. Beginning 24 hours after injection of the last dose, 4 calves were euthanized each day for 5 days. Plasma and tissue samples were analyzed by ultraperformance liquid chromatography. Pharmacokinetic parameters were calculated by compartmental and noncompartmental methods.

RESULTS Mean ± SD plasma flunixin elimination half-life, residence time, and clearance were 1.32 ± 0.94 hours, 12.54 ± 10.96 hours, and 64.6 ± 40.7 mL/h/kg, respectively. Mean hepatic and muscle flunixin concentrations decreased to below FDA-established tolerance limits (0.125 and 0.025 μg/mL, respectively) for adult cattle by 3 and 2 days, respectively, after injection of the last dose of flunixin. Detectable flunixin concentrations were present in both the liver and muscle for at least 5 days after injection of the last dose.

CONCLUSIONS AND CLINICAL RELEVANCE The labeled slaughter withdrawal interval for flunixin in adult cattle is 4 days. Because administration of flunixin to veal calves represents extralabel drug use, any detectable flunixin concentrations in edible tissues are considered a violation. Results indicated that a slaughter withdrawal interval of several weeks may be necessary to ensure that violative tissue residues of flunixin are not detected in veal calves treated with that drug.

Contributor Notes

Dr. Kissell's present address is Merck Animal Health, 2 Giralda Farms, Madison, NJ 07940.

Dr. Brinson's present address is Lander Veterinary Clinic, 4512 S Walnut Rd, Turlock, CA 95380.

Address correspondence to Dr. Smith (Geoffrey_Smith@ncsu.edu).