Clinical Drug Investigation

, Volume 11, Issue 6, pp 320–330 | Cite as

Analgesic Efficacy of Low Doses of Dexketoprofen in the Dental Pain Model

A Randomised, Double-Blind, Placebo-Controlled Study
  • C. Gay
  • E. Planas
  • M. Donado
  • J. M. Martínez
  • R. Artigas
  • F. Torres
  • David Mauleón
  • G. Carganico
Clinical Use

Summary

Dexketoprofen (S(+)-2-(3-benzoylphenyl)propionic acid) is the active enantiomer of ketoprofen, a racemic nonsteroidal anti-inflammatory drug with proven analgesic activity in the treatment of pain, including acute pain after dental surgery. The aim of this randomised, double-blind study was to compare the analgesic efficacy of single oral doses (5, 10 and 20mg) of the tromethamine salt of dexketoprofen (DKR.TRIS) [equivalent to 3.5, 7 and 14mg of dexketoprofen, respectively] with that of placebo in the dental pain model. Ibuprofen (400mg) was used to validate the model. A total of 206 patients experiencing moderate to severe pain after surgical removal of the impacted third molar tooth under local anaesthesia were entered in this trial at 2 centres. Patients rated their pain intensity and pain relief on verbal rating and visual analogue scales at regular intervals during the 6-hour period after drug administration. Patients were also requested to provide a global evaluation of treatment efficacy at the end of the observation period. DKR.TRIS (10 and 20mg) and ibuprofen were superior to placebo as determined by significantly higher values for the sum of the pain intensity difference scores and total pain relief scores from baseline. Furthermore, the time to reduce baseline pain by at least 50% was significantly more rapid in patients treated with DKR.TRIS (10 and 20mg) and ibuprofen than in placebo recipients. The mean time to remedication with rescue analgesia was significantly longer in all active treatment groups compared with placebo. DKR.TRIS was well tolerated, with a reported incidence of adverse events similar to that of placebo. No serious adverse events were reported in any treatment group. The results of this study suggest that DKR.TRIS is an effective analgesic with a favourable tolerability profile for the treatment of acute pain states.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ferreira SH, Vane JR. New aspects of the mode of action of non-steroidal anti-inflammatory drugs. Ann Rev Pharmacol 1974; 14: 57–73CrossRefGoogle Scholar
  2. 2.
    Vane JR. The mode of action of aspirin and similar compounds. Hosp Form 1976; 10: 618–29Google Scholar
  3. 3.
    Gleeson S, Sorbie J. Efficacy of ketoprofen in treating primary dysmenorrhea. Can Med Assoc J 1983; 129: 842–4PubMedGoogle Scholar
  4. 4.
    Sunshine A, Olson NZ. Analgesic efficacy of ketoprofen in postpartum, general surgery and chronic cancer pain. J Clin Pharmacol 1988; 28 Suppl.: 47–54Google Scholar
  5. 5.
    Turek MD, Baird WM. Double-blind parallel comparison of ketoprofen (Orudis), acetaminophen plus codeine, and placebo in postoperative pain. J Clin Pharmacol 1988; 28 Suppl.: 23–8Google Scholar
  6. 6.
    Fossgreen J. Ketoprofen. A survey of current publications. Scand J Rheumatol 1976; 14 Suppl.: 7–32Google Scholar
  7. 7.
    Serry MM. A low-dosage ketoprofen preparation in the management of osteoarthritis of the knee joint. J Int Med Res 1980; 8: 388–90PubMedGoogle Scholar
  8. 8.
    Muller-Fassbender H, Reiter W, Eveld H. Open multicenter long term trial (3 years) on efficacy and tolerance of ketoprofen (Orudis capsules) in rheumatology: final assessment. Curr Ther Res 1984; 36: 1221–7Google Scholar
  9. 9.
    van der Meij T, van Harten RPW. Evaluation of the efficacy and tolerance of Orudis 100mg in osteoarthritis in general practice. Clin Exp Rheumatol 1987; 5: 88Google Scholar
  10. 10.
    Fine IT. Clinical experience with ketoprofen in the managment of osteoarthritis and rheumatoid arthritis. Md Med J 1989; 38: 485–8PubMedGoogle Scholar
  11. 11.
    Cooper SA, Gelb SB, Cavaliere MBM, et al. An analgesic relative potency assay comparing ketoprofen and aspirin in postoperative dental pain. Adv Ther 1984; 1: 410–8Google Scholar
  12. 12.
    Mehlish D, Frakes L, Cavaliere MBM, et al. Double-blind parallel comparison of single oral doses of ketoprofen, codeine and placebo in patients with moderate to severe dental pain. J Clin Pharmacol 1984; 24: 486–92Google Scholar
  13. 13.
    Cooper SA, Berrie R, Cohn P. Comparison of ketoprofen, ibuprofen and placebo in dental pain surgery model. Adv Ther 1988; 5: 43–53Google Scholar
  14. 14.
    Caldwell J, Hutt AJ, Fournel-Gigleux S. The metabolic chiral inversion and dispositional enantioselectivity of the 2-arylpropionic acids and their biological consequences. Biochem Pharmacol 1988; 37: 105–14PubMedCrossRefGoogle Scholar
  15. 15.
    Evans AM. Enantioselective pharmacodynamics and pharma-cokinetics of chiral non-steroidal anti-inflammatory drugs. Eur J Clin Pharmacol 1992; 42: 237–56PubMedCrossRefGoogle Scholar
  16. 16.
    Palomer A, Cabré M, Ginesta J, et al. Resolution of rac-ketoprofen esters by enzymatic reactions in organic media. Chiraility 1993; 5: 320–8CrossRefGoogle Scholar
  17. 17.
    Moreno JJ, Calvo L, Fernández F, et al. Biological activity of ketoprofen and its optical isomers. Eur J Pharmacol 1990; 183: 2263–4CrossRefGoogle Scholar
  18. 18.
    Hayball PJ, Nation RL, Bochner F. Enantioselective pharmacodynamics of the nonsteroidal antiinflammatory drug ketoprofen: in vitro inhibition of human platelet cyclooxygenase activity. Chirality 1992; 4: 484–7PubMedCrossRefGoogle Scholar
  19. 19.
    Suesa N, Fernandez MF, Gutierrez M, et al. Stereoselective cyclooxygenase inhibition in cellular models by the enantiomers of ketoprofen. Chirality 1993; 5: 589–95PubMedCrossRefGoogle Scholar
  20. 20.
    Gich I, Barbanoj MJ, Artigas R, et al. New fast onset formulation of dexketoprofen. 6th Interscience World Conference on Inflammation, Antirheumatics Analgesics Immunomodulators 95: 1995 Mar 28–30: GenevaGoogle Scholar
  21. 21.
    Max MB, Laska EM. Single-dose analgesic comparisons. Max M, Portenoy R, Laska E, editors. Advances in pain research and therapy. Vol. 18, New York: Raven Press, 1991: 55–95Google Scholar
  22. 22.
    Dupont WD. Power and simple size calculations: a review and computer program. Con Clin Trials 1990; 11: 116–28CrossRefGoogle Scholar
  23. 23.
    Einot I, Gabriel KR. A study of the powers of several methods of multiple comparisons. J Am Stat Soc 1975; 70: 351Google Scholar
  24. 24.
    Lötsch J, Geisslinger G, Mohammadian P, et al. Effects of flurbiprofen enantiomers on pain-related chemosomatosensory evoked potentials in human subjects. Br J Clin Pharmacol 1995; 40: 339–46PubMedCrossRefGoogle Scholar
  25. 25.
    Aberg G, Ciofalo VB, Pendieton RG, et al. Inversion of (R)-to (S)-ketoprofen in eight animal species. Chirality 1995; 7: 383–7PubMedCrossRefGoogle Scholar
  26. 26.
    Calvo L, Fernández F, Ferrer X, et al. Analgesic action of ketoprofen enantiomers in animal models. Pharmacol Res 1995; 31 Suppl.: 257CrossRefGoogle Scholar
  27. 27.
    Cooper SA, Beaver WT. A model to evaluate mild analgesics in oral surgery outpatients. Clin Pharmacol Ther 1976; 20: 241–50PubMedGoogle Scholar
  28. 28.
    Cooper SA. Models for clinical assessment of oral analgesics. Am J Med 1983; 75: 24–9PubMedCrossRefGoogle Scholar
  29. 29.
    Guideline for the clinical evaluation of analgesic drugs. U.S. Department of Health and Human Services. Public Health Service, Food and Drug Administration, 1992Google Scholar

Copyright information

© Adis International Limited 1996

Authors and Affiliations

  • C. Gay
    • 1
  • E. Planas
    • 1
  • M. Donado
    • 2
  • J. M. Martínez
    • 2
  • R. Artigas
    • 3
  • F. Torres
    • 4
  • David Mauleón
    • 3
  • G. Carganico
    • 3
  1. 1.Facultad de OdontologíaUniversidad de BarcelonaBarcelonaSpain
  2. 2.Facultad de OdontologíaUniversidad Complutense de MadridMadridSpain
  3. 3.Departamento de R & DLaboratorios Menarini SABarcelonaSpain
  4. 4.Laboratorio de Bioestadística y EpidemiologíaUniversidad Autónoma de BarcelonaBarcelonaSpain
  5. 5.Laboratorios Menarini SABadalona (Barcelona)Spain

Personalised recommendations