Skip to main content
Log in

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

  • Published:
Veterinary Research Communications Aims and scope Submit manuscript

Abstract

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 T max = 0.76±0.19 h, C max = 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, V d/F = 0.39±0.07 L/kg, Cl/F = 170±39 ml/(kg.h). The mean (±SD) pharmacokinetic parameters of MLX were T max = 8.5±1.91 h, C max = 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, V d/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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  • 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, 383-387

    Google Scholar 

  • 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, 196-201

    Google Scholar 

  • 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, 695-701

    Google Scholar 

  • 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, 1755-1760

    Google Scholar 

  • 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, 576-584

    Google Scholar 

  • 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, 105-114

    Google Scholar 

  • Campbell, D.B., 1990. Stereoselectivity in clinical pharmacokinetics and drug development. European Journal of Drug Metabolism and Pharmacokinetics, 15, 109-125

    Google Scholar 

  • 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, 265-271

    Google Scholar 

  • 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, 626-631

    Google Scholar 

  • 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, 515-527

    Google Scholar 

  • Delatour, P., Benoit, E., Besse, S. and Soraci, A., 1994a. Asymetrie moleculare et pharmacologic comparée. Revue de Médicine Vétérinaire, 145, 551-561

    Google Scholar 

  • 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), 6-9

    Google Scholar 

  • 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, 946-951

    Google Scholar 

  • 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, 296-300

    Google Scholar 

  • 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), s5-9

    Google Scholar 

  • Evans, A.M., 1992. Enantioselective pharmacodynamics and pharmacokinetics of chiral non-steroidal anti-inflammatory drugs. European Journal of Clinical Pharmacology, 42, 237-256

    Google Scholar 

  • Flower, R.J. and Vane, J.R., 1974. Inhibition of prostaglandin biosynthesis. Biochemical Pharmacology, 23, 1439-1450

    Google Scholar 

  • Foster, R.T. and Jamali, F., 1987. High performance liquid chromatographic assay of ketoprofen enantiomers in human plasma and urine. Journal of Chromatography, 416, 388-393

    Google Scholar 

  • Gibaldi, M. and Perrier, D., 1982. Pharmacokinetics, 2nd edn, (Marcel Dekker, New York)

    Google Scholar 

  • 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, 1105-1110

    Google Scholar 

  • 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), s35-37

    Google Scholar 

  • Hawkey, C.J., 1999. COX-2 inhibitors. The Lancet, 353, 307-314

    Google Scholar 

  • 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, 185-193

    Google Scholar 

  • 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, 29-37

    Google Scholar 

  • 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, 841-862

    Google Scholar 

  • 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, 802-810

    Google Scholar 

  • Landoni, M.F. and Lees, P., 1996. Pharmacokinetics and pharmacodynamics of ketoprofen enantiomers in the horse. Journal of Veterinary Pharmacology and Therapeutics, 19, 466-476

    Google Scholar 

  • 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, 315-324

    Google Scholar 

  • 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, 349-359

    Google Scholar 

  • 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, 568-582

    Google Scholar 

  • 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, 1359-1375

    Google Scholar 

  • 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, 35-42

    Google Scholar 

  • Mehvar, R. and Jamali, F., 1988. Pharmacokinetic analysis of enantiomeric inversion of chiral nonsteroidal anti-inflammatory drugs. Pharmaceutical Research, 5, 76-79

    Google Scholar 

  • 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, 358-363

    Google Scholar 

  • 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, 1441-1446

    Google Scholar 

  • 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, 108-116

    Google Scholar 

  • Schmitt, M. and Guentert, T.W., 1990. Biopharmaceutical evaluation of ketoprofen following intravenous, oral, and rectal administration in dogs. Journal of Pharmaceutical Science, 79, 614-616

    Google Scholar 

  • 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 

  • Soraci, A., Tapia, O., Castro, E. and San Martin, M.F., 1996. Asimetría molecular: importancia de su conocimiento. Acta Bioquímica Clínica Latinoamericana, 3, 151-163

    Google Scholar 

  • Vane, J.R. and Botting, R.M., 1998. Mechanism of action of nonsteroidal antinflammatory drugs. American Journal of Medicine, 194, 2S-8S.

    Google Scholar 

  • 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, 807-811

    Google Scholar 

  • 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, 431-436

    Google Scholar 

  • 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, 165-175

    Google Scholar 

  • 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, 2947-2954

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Montoya, L., Ambros, L., Kreil, V. et al. A Pharmacokinetic Comparison of Meloxicam and Ketoprofen following Oral Administration to Healthy Dogs. Vet Res Commun 28, 415–428 (2004). https://doi.org/10.1023/B:VERC.0000034995.81994.49

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:VERC.0000034995.81994.49

Navigation