Pharmacokinetics of intravenously and orally administered meloxicam in sheep

Matthew L. Stock Department of Clinical Studies, School of Veterinary Medicine, New Bolton Center, University of Pennsylvania, Kennett Square, PA 19348.

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Johann F. Coetzee Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Butch KuKanich Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Billy I. Smith Department of Clinical Studies, School of Veterinary Medicine, New Bolton Center, University of Pennsylvania, Kennett Square, PA 19348.

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Abstract

Objective—To determine the pharmacokinetics of meloxicam after IV and PO administration to 6 healthy sheep.

Animals—6 healthy adult Dorset cross sheep (5 males and 1 female).

Procedures—Meloxicam (0.5 mg/kg, IV, or 1.0 mg/kg, PO) was administered in a randomized crossover design with a 10-day washout period. Blood samples were collected at predetermined times over 96 hours. Serum drug concentrations were determined by high-pressure liquid chromatography with mass spectrometry. Computer software was used to estimate values of pharmacokinetic parameters through noncompartmental methods.

Results—Following IV administration (n = 5), the geometric mean (range) elimination half-life was 14.0 hours (10.5 to 17.0 hours), volume of distribution was 0.204 L/kg (0.171 to 0.272 L/kg), and clearance was 0.17 mL/min/kg (0.12 to 0.27 mL/min/kg). Following oral administration (n = 6), maximum serum concentration was 1.72 μg/mL (1.45 to 1.93 μg/mL), time to maximum serum concentration was 19.0 hours (12.0 to 24.0 hours), clearance per bioavailability was 0.22 mL/min/kg (0.16 to 0.30 mL/min/kg), and terminal half-life was 15.4 hours (13.2 to 17.7 hours). Bioavailability of orally administered meloxicam was calculated as 72% (40% to 125%; n = 5). No adverse effects were evident following meloxicam administration via either route.

Conclusions and Clinical Relevance—Meloxicam administered PO at 1.0 mg/kg has good bioavailability with slow elimination kinetics in sheep. These data suggested that meloxicam may be clinically useful, provided the safety and analgesic efficacy of meloxicam as well as feed-related influences on its pharmacokinetics are established in ruminants.

Abstract

Objective—To determine the pharmacokinetics of meloxicam after IV and PO administration to 6 healthy sheep.

Animals—6 healthy adult Dorset cross sheep (5 males and 1 female).

Procedures—Meloxicam (0.5 mg/kg, IV, or 1.0 mg/kg, PO) was administered in a randomized crossover design with a 10-day washout period. Blood samples were collected at predetermined times over 96 hours. Serum drug concentrations were determined by high-pressure liquid chromatography with mass spectrometry. Computer software was used to estimate values of pharmacokinetic parameters through noncompartmental methods.

Results—Following IV administration (n = 5), the geometric mean (range) elimination half-life was 14.0 hours (10.5 to 17.0 hours), volume of distribution was 0.204 L/kg (0.171 to 0.272 L/kg), and clearance was 0.17 mL/min/kg (0.12 to 0.27 mL/min/kg). Following oral administration (n = 6), maximum serum concentration was 1.72 μg/mL (1.45 to 1.93 μg/mL), time to maximum serum concentration was 19.0 hours (12.0 to 24.0 hours), clearance per bioavailability was 0.22 mL/min/kg (0.16 to 0.30 mL/min/kg), and terminal half-life was 15.4 hours (13.2 to 17.7 hours). Bioavailability of orally administered meloxicam was calculated as 72% (40% to 125%; n = 5). No adverse effects were evident following meloxicam administration via either route.

Conclusions and Clinical Relevance—Meloxicam administered PO at 1.0 mg/kg has good bioavailability with slow elimination kinetics in sheep. These data suggested that meloxicam may be clinically useful, provided the safety and analgesic efficacy of meloxicam as well as feed-related influences on its pharmacokinetics are established in ruminants.

Contributor Notes

Drs. Stock and Coetzee's present address is Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

Supported by the Frances Cheney Glover Endowment Fund, School of Veterinary Medicine, University of Pennsylvania.

The authors thank Drs. Michaela Kristula, Jonathan Garber, Olivia Schroeder, Laura Barth, and Jordan Shelton for technical assistance.

Address correspondence to Dr. Stock (mstock@iastate.edu).
  • 1. Yocum D, Fleischmann R, Dalgin P, et al. Safety and efficacy of meloxicam in the treatment of osteoarthritis: a 12-week, double-blind, multiple-dose, placebo-controlled trial. The Meloxicam Osteoarthritis Investigators. Arch Intern Med 2000; 160:29472954.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Carroll GL, Narbe R, Kerwin SC, et al. Dose range finding study for the efficacy of meloxicam administered prior to sodium urate-induced synovitis in cats. Vet Anaesth Analg 2011; 38:394406.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Cross AR, Budsberg SC, Keefe TJ. Kinetic gait analysis assessment of meloxicam efficacy in a sodium urate-induced synovitis model in dogs. Am J Vet Res 1997; 58:626631.

    • Search Google Scholar
    • Export Citation
  • 4. Toutain PL, Cester CC. Pharmacokinetic-pharmacodynamic relationships and dose response to meloxicam in horses with induced arthritis in the right carpal joint. Am J Vet Res 2004; 65:15331541.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Lehr T, Narbe R, Jons O, et al. Population pharmacokinetic modelling and simulation of single and multiple dose administration of meloxicam in cats. J Vet Pharmacol Ther 2010; 33:277286.

    • Search Google Scholar
    • Export Citation
  • 6. Montoya L, Ambros L, Kreil V, et al. A pharmacokinetic comparison of meloxicam and ketoprofen following oral administration to healthy dogs. Vet Res Commun 2004; 28:415428.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Toutain PL, Reymond N, Laroute V, et al. Pharmacokinetics of meloxicam in plasma and urine of horses. Am J Vet Res 2004; 65:15421547.

  • 8. Giraudel JM, Diquelou A, Laroute V, et al. Pharmacokinetic/pharmacodynamic modeling of NSAIDs in a model of reversible inflammation in the cat. Br J Pharmacol 2005; 146:642653.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Coetzee J, Kukanich B, Mosher R, et al. Pharmacokinetics of intravenous and oral meloxicam in ruminant calves. Vet Ther 2009; 10:E1E8.

  • 10. Coetzee JF, Mosher RA, Kohake LE, et al. Pharmacokinetics of oral gabapentin alone or co-administered with meloxicam in ruminant beef calves. Vet J 2011; 190:98102.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Ingvast-Larsson C, Hogberg M, Mengistu U, et al. Pharmacokinetics of meloxicam in adult goats and its analgesic effect in disbudded kids. J Vet Pharmacol Ther 2011; 34:6469.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. 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; 51:14641467.

    • Search Google Scholar
    • Export Citation
  • 13. Welsh EM, McKellar QA, Nolan AM. The pharmacokinetics of flunixin meglumine in the sheep. J Vet Pharmacol Ther 1993; 16:181188.

  • 14. Lees P, Giraudel J, Landoni MF, et al. PK-PD integration and PK-PD modelling of nonsteroidal anti-inflammatory drugs: principles and applications in veterinary pharmacology. J Vet Pharmacol Ther 2004; 27:491502.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Shukla M, Singh G, Sindhura BG, et al. Comparative plasma pharmacokinetics of meloxicam in sheep and goats following intravenous administration. Comp Biochem Physiol C Toxicol Pharmacol 2007; 145:528532.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. Colditz IG, Paull DR, Hervault G, et al. Development of a lameness model in sheep for assessing efficacy of analgesics. Aust Vet J 2011; 89:297304.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Paull DR, Lee C, Atkinson SJ, et al. Effects of meloxicam or tolfenamic acid administration on the pain and stress responses of Merino lambs to mulesing. Aust Vet J 2008; 86:303311.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Turck D, Roth W, Busch U. A review of the clinical pharmacokinetics of meloxicam. Br J Rheumatol 1996; 35 (suppl 1):1316.

  • 19. Busch U, Schmid J, Heinzel G, et al. Pharmacokinetics of meloxicam in animals and the relevance to humans. Drug Metab Dispos 1998; 26:576584.

    • Search Google Scholar
    • Export Citation
  • 20. Pellegrini-Masini A, Poppenga RH, Sweeney RW. Disposition of flunixin meglumine injectable preparation administered orally to healthy horses. J Vet Pharmacol Ther 2004; 27:183186.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Welsh JC, Lees P, Stodulski G, et al. Influence of feeding schedule on the absorption of orally administered flunixin in the horse. Equine Vet J Suppl 1992;(11):6265.

    • Search Google Scholar
    • Export Citation
  • 22. Lees P, Taylor JB, Higgins AJ, et al. In vitro and in vivo binding of phenylbutazone and related drugs to equine feeds and digesta. Res Vet Sci 1988; 44:5056.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Lees P, Ayliffe T, Maitho TE, et al. Pharmacokinetics, metabolism and excretion of phenylbutazone in cattle following intravenous, intramuscular and oral administration. Res Vet Sci 1988; 44:5767.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Cheng Z, McKeller Q, Nolan A. Pharmacokinetic studies of flunixin meglumine and phenylbutazone in plasma, exudate and transudate in sheep. J Vet Pharmacol Ther 1998; 21:315321.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Szotakova B, Baliharova V, Lamka J, et al. Comparison of in vitro activities of biotransformation enzymes in pig, cattle, goat and sheep. Res Vet Sci 2004; 76:4351.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. US FDA. Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA). Available at: www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/AnimalMedicinalDrugUseClarificationActAMDUCAof1994/default.htm. Accessed Aug 13, 2012.

    • Search Google Scholar
    • Export Citation
  • 27. Smith GW, Davis JL, Tell LA, et al. Extralabel use of nonsteroidal anti-inflammatory drugs in cattle. J Am Vet Med Assoc 2008; 232:697701.

  • 28. Riviere JE, Webb AI, Craigmill AL. Primer on estimating withdrawal times after extralabel drug use. J Am Vet Med Assoc 1998; 213:966968.

    • Search Google Scholar
    • Export Citation

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