European Journal of Clinical Pharmacology

, Volume 18, Issue 5, pp 407–414 | Cite as

Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration

  • T. Ishizaki
  • T. Sasaki
  • T. Suganuma
  • Y. Horai
  • K. Chiba
  • M. Watanabe
  • W. Asuke
  • H. Hoshi


The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC]0 after rectal administration of a suppository showed the minimum significant difference (p<0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.

Key words

ketoprofen pharmacokinetics relative bioavailability single doses repeated doses prediction of kinetics 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cathcart BJ, Vince JD, Gordon AJ, Bell MA, Chalmers IM (1973) Studies on 2-(3-benzoylphenyl) propionic acid (Orudis). A double-blind crossover trial in patients with rheumatoid arthritis and an assessment of its influence on hepatic drug-metabolizing enzymes. Ann Rheum Dis 32: 62–65Google Scholar
  2. 2.
    Mitchell WS, Scott P, Kennedy AC, Brooks PM, Templeton R, Jeffries MG (1975) Clinico-pharmacological studies on ketoprofen (‘Orudis’). Curr Med Res Opin 3: 423–430Google Scholar
  3. 3.
    Huskisson EC, Woolfe DL, Balme HW, Scott J, Franklyn S (1976) Four new anti-inflammatory drugs: responses and variations. Br Med J 1: 1048–1049Google Scholar
  4. 4.
    Lee P, Anderson JA, Miller J, Webb J, Buchanan WW (1976) Evaluation of analgesic action and efficacy of antirheumatic drugs. Study of 10 drugs in 684 patients with rheumatoid arthritis. J Rheumatol 3: 283–294Google Scholar
  5. 5.
    Mills SB, Bloch M, Bruckner FE (1973) Double-blind cross-over study of ketoprofen and ibuprofen in management of rheumatoid arthritis. Br Med J 4: 82–84Google Scholar
  6. 6.
    Fossgreen J (1976) Ketoprofen. A survey of current publications. Scand J Rheumatol 14 (Suppl): 11–32Google Scholar
  7. 7.
    Gregoire J, Pasquier P, Populaire P, Renard A, Heusse D (1977) Pharmacokinetic study of ketoprofen and of its bioavailability by oral route in man. Abstract of XIV International Congress of Rheumatology, San Francisco CA, p 72Google Scholar
  8. 8.
    Lewellen ORW, Templeton R (1976) The pharmacokinetics of ketoprofen in man during and after repeated oral dosing (50 mg q.i.d.) with Orudis®. Scand J Rheumatol 14 (Suppl): 53–62Google Scholar
  9. 9.
    Queneau P, Amourdedieu J, Daumont A (1976) Clinical study of ketoprofen administered rectally in rheumatology. Rheumatol Rehabil 15 (Suppl): 61–64Google Scholar
  10. 10.
    Gougeon J, Mireau-Hottin J, Gaillard F (1976) Clinical trial of the injectable form of ketoprofen. Rheumatol Rehabil 15 (Suppl): 75–78Google Scholar
  11. 11.
    Nuttall FQ, Wedin DS (1966) A simple rapid colorimetric method for determination of creatine kinase activity. J Lab Clin Med 68: 324–332Google Scholar
  12. 12.
    Populaire P, Terlain B, Pascal S, Decouvelaere B, Lebreton G, Renard A, Thomas JP (1973) Dosage de l'acide (benzoyl-3 phenyl)-2 propionique ou ketoprofen dans les milieux bioloques. Ann Pharm Fr 31: 679–688Google Scholar
  13. 13.
    Wagner JG (1975) Linear compartment models. In: Fundamentals of clinical pharmacokinetics, first edition. Drug Intelligence Publications, Hamilton IL, pp 57–128Google Scholar
  14. 14.
    Sedman AJ, Wagner JG (1974–7) Autoan manual. Autoan is a decision-making pharmacokinetic digital computer program. Nov 1974–April 1977. Distributed by Publication Distribution Service, 610E, University Avenue Ann Arbor MI 48106Google Scholar
  15. 15.
    Greenblatt DJ, Koch-Weser J (1975) Clinical pharmacokinetics II. N Engl J Med 293: 964–970Google Scholar
  16. 16.
    Wagner JG (1972) An overview of the analysis and interpretation of bioavailability studies in man. Pharmacology 8: 102–117Google Scholar
  17. 17.
    Wagner JG, Metzler CM (1969) Prediction of blood levels after multiple doses from single-dose blood level data: data generated with two-compartment open models analyzed according to the one-compartment open model. J Pharm Sci 58: 87–92Google Scholar
  18. 18.
    Wagner JG, Northam JI, Alway CD, Carpenter OS (1965) Blood levels of drug at the equilibrium state after multiple dosing. Nature 207: 1301–1302Google Scholar
  19. 19.
    Wagner JG (1967) Drug accumulation. J Clin Pharmacol 7: 84–88Google Scholar
  20. 20.
    Delbarre F, Roucayrol JC, Amor B, Ingrand J, Bourat G, Fournel J, Courjaret J (1976) Pharmacokinetic study of ketoprofen (19.583 R.P.) in man using the tritiated compound. Scand J Rheumatol 14 (Suppl): 45–52Google Scholar
  21. 21.
    Brodgen RN, Pinder RM, Speight TM, Avery GS (1977) Fenoprofen. A review of its pharmacological properties and therapeutic efficacy in rheumatic diseases. Drugs 13: 241–265Google Scholar
  22. 22.
    Champion GD, Graham GG (1978) Pharmacokinetics of nonsteroidal anti-inflammatory agents. Aust NZ J Med 8 (Suppl 1): 94–100Google Scholar
  23. 23.
    Ishizaki T, Nomura T, Abe T (1979) Pharmacokinetics of piroxicam, a new nonsteroidal anti-inflammatory agent under fasting and postprandial states in man. J. Pharmacokinet Biopharm 7: 369–381Google Scholar
  24. 24.
    Selley ML, Glass J, Triggs EJ, Thomas J (1975) Pharmacokinetic studies of tolmetin in man. Clin Pharmacol Ther 17: 599–605Google Scholar
  25. 25.
    Vesell ES (1974) Relationship between drug distribution and therapeutic effects in man. Annu Rev Pharmacol 14: 249–270Google Scholar
  26. 26.
    Heusse D, Populaire P (1977) The metabolic disposition of3H-ketoprofen in various species. Abstract of XIV International Congress of Rheumatology, San Francisco CA, p 72Google Scholar
  27. 27.
    Greenblatt DJ, Koch-Weser J (1976) Intramuscular injection of drugs. N Engl J Med 295: 542–546Google Scholar
  28. 28.
    Sidell FR, Culver DL, Kaminskis A (1974) Serum creatine phosphokinase activity after intramuscular injection: the effect of dose, concentration, and volume. J Am Med Assoc 229: 1894–1897Google Scholar
  29. 29.
    Alvan G, Orme M, Bertilsson L, Ekstrand R, Palmer L (1975) Pharmacokinetics of indomethacin. Clin Pharmacol Ther 18: 364–373Google Scholar
  30. 30.
    Holt LPJ, Hawkins CF (1965) Indomethacin: Studies of absorption and of the use of indomethacin suppositories. Br Med J 1: 1354–1356Google Scholar
  31. 31.
    Huskisson EC, Taylor RT, Burston D, Chuter PJ, Dudley HF (1970) Evening indomethacin in the treatment of rheumatoid arthritis. Ann Rheum Dis 29: 393–396Google Scholar
  32. 32.
    Chen W, Vrindten PA, Dayton RG, Burn JJ (1962) Accelerated aminopyrine metabolism in human subjects pretreated with phenylbutazone. Life Sci 2: 35–42Google Scholar
  33. 33.
    Chalmers TM, Bell MA, Buchanan WW (1973) Effect of flurbiprofen on the metabolism of antipyrine in man. Ann Rheum Dis 32: 58–60Google Scholar
  34. 34.
    Rubin A, Rodda BE, Warrick P, Ridolfo A, Gruber CM (1971) Physiological disposition of fenoprofen in man I: Pharmacokinetic comparison of calcium and sodium salts administered orally. J Pharm Sci 60: 1797–1801Google Scholar
  35. 35.
    Runkel R, Chaplin M, Boost G, Segre E, Forchielli E (1972) Absorption, distribution, metabolism, and excretion of naproxen in various laboratory animals and human subjects. J Pharm Sci 61: 703–708Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • T. Ishizaki
    • 1
  • T. Sasaki
    • 1
  • T. Suganuma
    • 1
  • Y. Horai
    • 1
  • K. Chiba
    • 1
  • M. Watanabe
    • 1
  • W. Asuke
    • 2
  • H. Hoshi
    • 3
  1. 1.Division of Clinical Pharmacology, Clinical Research InstituteNational Medical Center HospitalTokyoJapan
  2. 2.Department of Biochemical Pharmacology, Faculty of Pharmaceutical ScienceUniversity of ChibaChibaJapan
  3. 3.Department of Pharmaceutical ChemistryKyoto College of PharmacyKyotoJapan

Personalised recommendations