Veterinary Research Communications

, Volume 28, Issue 5, pp 415–428 | Cite as

A Pharmacokinetic Comparison of Meloxicam and Ketoprofen following Oral Administration to Healthy Dogs

  • L. Montoya
  • L. Ambros
  • V. Kreil
  • R. Bonafine
  • G. Albarellos
  • R. Hallu
  • A. Soraci


Ketoprofen (KTP) and meloxicam (MLX) are non-steroidal anti-inflamatory drugs used extensively in veterinary medicine. The pharmacokinetics of these drugs were studied in eight dogs following a single oral dose of 1 mg/kg of KTP as a racemate or 0.2 mg/kg of MLX. The concentrations of the drugs in plasma were determined by high-performance liquid chromatography (HPLC). There were differences between the disposition curves of the KTP enantiomers, confirming that the pharmacokinetics of KTP is enantioselective. (S)-(+)-KTP was the predominant enantiomer; the S:R ratio in the plasma increased from 2.58±0.38 at 15 min to 5.72±2.35 at 1 h. The area under the concentration–time curve (AUC) of (S)-(+)-KTP was approximately 6 times greater than that of (R)-(–)-KTP. The mean (±SD) pharmacokinetic parameters for (S)-(+)-KTP were characterized as Tmax = 0.76±0.19 h, Cmax = 2.02±0.41 μg/ml, t\(t_{\frac{1}{2}{\text{el}}} \) = 1.65±0.48 h, AUC = 6.06±1.16 μg.h/ml, Vd/F = 0.39±0.07 L/kg, Cl/F = 170±39 ml/(kg.h). The mean (±SD) pharmacokinetic parameters of MLX were Tmax = 8.5±1.91 h, Cmax = 0.82±0.29 μg/ml, t\(t_{\frac{1}{2}\lambda ({\text{z)}}} \) = 12.13±2.15 h, AUCinf = 15.41±1.24 μg.h/ml, Vd/F = 0.23±0.03 L/kg, and Cl/F = 10±1.4 ml/(kg.h). Our results indicate significant pharmacokinetic differences between MLX and KTP after therapeutic doses.

dogs ketoprofen meloxicam NSAID pharmacokinetics 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aberg, G., Ciofalo, V.B., Pendleton, R.G., Ray, G. and Weddle, D., 1995. Inversion of (R)-(−) to S ketoprofen in eight animals species. Chirality, 7, 383-387Google Scholar
  2. Armstrong, S., Tricklebank, P., Lake, A., Frean, S. and Lees, P., 1999. Pharmacokinetics of carprofen enantiomers in equine plasma and synovial fluid — a comparison with ketoprofen. Journal of Veterinary Pharmacology and Therapeutics, 22, 196-201Google Scholar
  3. Berry, B.W. and Jamali, F., 1991. Presystemic and systemic chiral inversion of R(–) fenoprofen in the rat. Journal of Pharmacology and Experimental Therapeutics, 258, 695-701Google Scholar
  4. Brideau, C., Van Staden, C. and Chung Chan, Ch., 2001. In vitro effects of cycloxygenase inhibitors in whole blood of horses, dogs, and cats. American Journal of Veterinary Research, 62, 1755-1760Google Scholar
  5. Busch, U., Schmid, J., Heinzel, G., Schmaus, H., Baierl, J., Huber, C. and Roth, W., 1998. Pharmacokinetics of meloxicam in animals and the relevance to humans. Drug Metabolism and Disposition, 26, 576-584Google Scholar
  6. Caldwell, J., Hutt, A.J. and Fournel-Gigleux, S., 1988. The metabolic chiral inversion and dispositional enantioselectivity of the 2-arylpropionic acids and their biological consequences. Biochemical Pharmacology, 37, 105-114Google Scholar
  7. Campbell, D.B., 1990. Stereoselectivity in clinical pharmacokinetics and drug development. European Journal of Drug Metabolism and Pharmacokinetics, 15, 109-125Google Scholar
  8. Castro, E., Soraci, A., Fogel, F. and Tapia, O., 2000. Chiral inversion of (R)-(−) fenoprofen and ketoprofen enantiomers in cats. Journal of Veterinary Pharmacology and Therapeutics, 23, 265-271Google Scholar
  9. Cross, A.R., Budsberg, S.C. and Keefe, J.T., 1997. Kinetic gait analysis assessment of meloxicam efficacy in a sodium urate-induced synovitis model in dogs. American Journal of Veterinary Research, 58, 626-631Google Scholar
  10. Delatour, P., Benoit, E., Bourdin, M., Gobron, M. and Moysan, F., 1993. Enantioselective comparée de la disposition de deux anti-inflammatoires non stéroidiens, le ketoprofene et le carprofene, chez l'homme et l'animal. Bulletin de l'Académie Nationale de Médicine, 177, 515-527Google Scholar
  11. Delatour, P., Benoit, E., Besse, S. and Soraci, A., 1994a. Asymetrie moleculare et pharmacologic comparée. Revue de Médicine Vétérinaire, 145, 551-561Google Scholar
  12. Delatour, P., Benoit, E., Besse, S. and Soraci, A., 1994b. Ruckebush Memorial Lecture: Drug chirality: its significance in veterinary pharmacology and therapeutics. In: P. Lees (ed.), Proceedings of the 6th International Congress of the European Association for Veterinary Pharmacology and Toxicology, (Blackwell Scientific, Edinburgh), 6-9Google Scholar
  13. Dequeker, J., Hawkey, C., Kahan, A., Steinbrück, K., Alegre, C., Baumelou, E., Bégaud, B., Isomäki, H., Littlejohn, G., Mau, J. and Papazoglou, S., 1998. Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the safety and efficacy large-scale evaluation of COX-inhibiting therapies (select) trial in osteoarthritis. British Journal of Rheumatology, 37, 946-951Google Scholar
  14. Doig, P.A., Purbrick, K.A., Hare, J.E. and McKeown, D.B., 2000. Clinical efficacy and tolerance of meloxicam in dogs with chronic osteoarthritis. Canine Veterinary Journal, 41, 296-300Google Scholar
  15. Euller-Ziegler, L., Velicitat, P., Bluhmki, E., Turck D., Scheuerer S. and Combe B., 2001. Meloxicam: a review of its pharmacokinetics, efficacy and tolerability following intramuscular administration. Inflammation Research, 50(supplement 1), s5-9Google Scholar
  16. Evans, A.M., 1992. Enantioselective pharmacodynamics and pharmacokinetics of chiral non-steroidal anti-inflammatory drugs. European Journal of Clinical Pharmacology, 42, 237-256Google Scholar
  17. Flower, R.J. and Vane, J.R., 1974. Inhibition of prostaglandin biosynthesis. Biochemical Pharmacology, 23, 1439-1450Google Scholar
  18. Foster, R.T. and Jamali, F., 1987. High performance liquid chromatographic assay of ketoprofen enantiomers in human plasma and urine. Journal of Chromatography, 416, 388-393Google Scholar
  19. Gibaldi, M. and Perrier, D., 1982. Pharmacokinetics, 2nd edn, (Marcel Dekker, New York)Google Scholar
  20. Grisneaux, E., Pibarot, P., Dupuis, J. and Blais, D., 1999. Comparison of ketoprofen and carprofen administered prior to orthopedic surgery for control of postoperative pain in dogs. Journal of American Veterinary Medicine Association, 215, 1105-1110Google Scholar
  21. Hanft G., Turck D., Scheuerer S. and Sigmund R., 2001. Meloxicam oral suspension: a treatment alternative to solid meloxicam formulation. Inflammation Research, 50(supplement 1), s35-37Google Scholar
  22. Hawkey, C.J., 1999. COX-2 inhibitors. The Lancet, 353, 307-314Google Scholar
  23. Hayball, P.J., Nation, R.L., Bochner, F., Sansom, L.N., Ahern, M.J. and Smith, M.D., 1993. The influence of renal function on the enantioselective pharmacokinetics of ketoprofen in patients with rheumatoid arthritis. British Journal of Clinical Pharmacology, 36, 185-193Google Scholar
  24. Igarza, L., Soraci, A., Auza, N. and Ceballos, H., 2002. Chiral inversion (R)-ketoprofen: influence of age and differing physiological status in dairy cattle. Veterinary Research Communications, 26, 29-37Google Scholar
  25. Johnston, S.A. and Budsberg, C.S., 1997. Nonsteroidal anti-inflammatory drugs and corticosteroids for the management of canine osteoarthritis. Veterinary Clinics of North America: Small Animal Practice, 27, 841-862Google Scholar
  26. Kay-Mugford, P., Benn, S., Lamarre, J. and Conlon, P., 2000. In vitro effects of nonsteroidal anti-inflammatory drugs on cyclooxygenase activity in dogs. American Journal of Veterinary Research, 61, 802-810Google Scholar
  27. Landoni, M.F. and Lees, P., 1996. Pharmacokinetics and pharmacodynamics of ketoprofen enantiomers in the horse. Journal of Veterinary Pharmacology and Therapeutics, 19, 466-476Google Scholar
  28. Landoni, M.F., Cunningham, F.M. and Lees, P., 1995. Pharmacokinetics and pharmacodynamics of ketoprofen in calves applying Pk/Pd modelling. Journal of Veterinary Pharmacology and Therapeutics, 18, 315-324Google Scholar
  29. Landoni, M.F., Comas, W., Mucci, N., Anglarilli, G., Bidal, D. and Lees, P., 1999. Enantiospecific pharmacokinetics and pharmacodynamics of ketoprofen in sheep. Journal of Veterinary Pharmacology and Therapeutics, 22, 349-359Google Scholar
  30. Lascelles, B.D.X., Cripps, P.J., Jones, A. and Waterman-Pearson, A.E., 1998. Efficacy and kinetics of carprofen, administered preoperatively or postoperatively, for the prevention of pain in dogs undergoing ovariohysterectomy. Veterinary Surgery, 27, 568-582Google Scholar
  31. Laudanno, O.M., Cesorali, J.A., Esnarriaga, J., San Miguel, P. and Bedini, O.A., 2000. In vivo selectivity of nonsteroidal antiinflammatory drugs and gastrointestinal ulcers in rats. Digestive Diseases and Sciences, 45, 1359-1375Google Scholar
  32. Martin, R.M., Biswas, P. and Mann, R.D., 2000. The incidence of adverse events and risk factors for upper gastrointestinal disorders associated with meloxicam use amongst 19087 patients in general practice in England: cohort study. British Journal of Clinical Pharmacology, 50, 35-42Google Scholar
  33. Mehvar, R. and Jamali, F., 1988. Pharmacokinetic analysis of enantiomeric inversion of chiral nonsteroidal anti-inflammatory drugs. Pharmaceutical Research, 5, 76-79Google Scholar
  34. Musser, J.M.B., Anderson, K.L. and Tyczkowska, K.L., 1998. Pharmacokinetic parameters and milk concentrations of ketoprofen after administration as a single intravenous bolus dose to lactating goats. Journal of Veterinary Pharmacology and Therapeutics, 21, 358-363Google Scholar
  35. Ricketts, A.P., Lundy, K.M. and Seibel, S.B., 1998. Evaluation of selective inhibition of canine cycloxigenase 1 and 2 by carprofen and other nonsteroidal anti-inflammatory drugs. American Journal of Veterinary Research, 59, 1441-1446Google Scholar
  36. Sams, R., Garken, D.F. and Asheraft, S.M., 1995. Pharmacokinetics of ketoprofen after multiple intravenous doses to mares. Journal of Veterinary Pharmacology and Therapeutics, 18, 108-116Google Scholar
  37. Schmitt, M. and Guentert, T.W., 1990. Biopharmaceutical evaluation of ketoprofen following intravenous, oral, and rectal administration in dogs. Journal of Pharmaceutical Science, 79, 614-616Google Scholar
  38. Soraci, A., 1995. Metabolisation stereoselective comparee des acides aryl-2-propioniques. Inversion chirale et glucuronoconjugaison, (Presentee devant l'Université Claude Bernard-Lyon en unie de l'Obtention du Diplome de Doctorat. Lyon, France)Google Scholar
  39. Soraci, A., Tapia, O., Castro, E. and San Martin, M.F., 1996. Asimetría molecular: importancia de su conocimiento. Acta Bioquímica Clínica Latinoamericana, 3, 151-163Google Scholar
  40. Vane, J.R. and Botting, R.M., 1998. Mechanism of action of nonsteroidal antinflammatory drugs. American Journal of Medicine, 194, 2S-8S.Google Scholar
  41. Vasseur, P.B., Johnson, A.L., Budsberg, S.C., Lincoln, J.D., Tooms, J.P., Whitehair, J.G. and Lentz, E.L., 1995. Randomized, controlled trial of the efficacy of carprofen, a nonsteroidal anti-inflammatory drug, in the treatment of osteoarthritis in dogs. Journal of the American Veterinary Medicine Association, 206, 807-811Google Scholar
  42. Velpandian, T., Jaiswal, J., Bhardwaj, R.K. and Gupta, S.K., 2000. Development and validation of a new high-performance liquid chromatographic estimation method of meloxicam in biological samples. Journal of Chromatography B. Biomedical Applications, 738, 431-436Google Scholar
  43. Yamaoka, K., Nakagawa, T. and Uno, T., 1978. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. Journal of Pharmaceutics and Biopharmaceutics, 6, 165-175Google Scholar
  44. Yocum, D., Fleischmann, R., Dalgin, P., Caldwell, J., Hall, D. and Roszko, P., 2000. Safety and efficacy of meloxicam in the treatment of osteoarthritis. Archives of Internal Medicine, 160, 2947-2954Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • L. Montoya
    • 1
  • L. Ambros
    • 1
  • V. Kreil
    • 1
  • R. Bonafine
    • 1
  • G. Albarellos
    • 1
  • R. Hallu
    • 1
  • A. Soraci
    • 2
  1. 1.Area de Farmacología, Facultad de Ciencias VeterinariasUniversidad de Buenos AiresBuenos AiresArgentina
  2. 2.Area de Toxicología, Facultad de Ciencias VeterinariasUniversidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA)Tandil, Buenos AiresArgentina

Personalised recommendations