Pharmaceutical Research

, Volume 18, Issue 7, pp 980–986 | Cite as

Comparison of Tissue Concentrations After Intramuscular and Topical Administration of Ketoprofen

  • Irmgard Tegeder
  • Jörn Lötsch
  • Martina Kinzig-Schippers
  • Fritz Sörgel
  • Gary R. Kelm
  • Stephen T. Meller
  • Gerd Geisslinger


Purpose. To assess whether topical ketoprofen, which has been reported to provide analgesic effects in clinical studies, reaches predictable tissue concentrations high enough to account for the reported analgesia. Intramuscular ketoprofen was used as positive control.

Methods. Muscle and subcutaneous tissue concentrations were assessed by microdialysis. Plasma and tissue concentrations after intramuscular injection were described using a three-compartment population pharmacokinetic model. The prediction performance of the model was assessed by superimposing tissue concentrations of 12 subjects that did not participate in the present study.

Results. Most dialysate concentrations after topical dosing of ketoprofen (100 mg) were below the quantification limit of 0.47 ng/ml. Plasma concentrations increased slowly and reached an apparent plateau of 7-40 ng/ml at 10-12h. No decline was observed up to 16 h. Tissue concentrations after intramuscular injection (100 mg) were about 10 times higher than those after topical dosing. Tissue concentrations measured in the majority of the 12 subjects that did not participate in the present study were found within the range of two-thirds of the predicted concentrations.

Conclusion. Predictable and cyclooxygenase-inhibiting concentrations of ketoprofen were achieved in subcutaneous and muscle tissue after intramuscular but not after topical dosing. Thus, the tissue concentrations of ketoprofen after topical administration can hardly explain the reported clinical efficacy of topical ketoprofen.

microdialysis ketoprofen NSAIDs topical administration population pharmacokinetic model 


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  1. 1.
    J. N. Cashman. The mechanisms of action of NSAIDs in analgesia. Drugs 5:13-23 (1996).Google Scholar
  2. 2.
    S. J. Brady, P. Brooks, P. Conaghan, and L. M. Kenyon. Pharmacotherapy and osteoarthritis. Baillieres Clin. Rheumatol. 11: 749-768 (1997).Google Scholar
  3. 3.
    E. M. Veys. 20 years' experience with ketoprofen. Scand. J. Rheumatol. Suppl. 90:1-44 (1991).Google Scholar
  4. 4.
    D. Henry, L. L. Lim, L.A. Garcia Rodriguez, et al. Variability in risk of gastrointestinal complications with individual nonsteroidal anti-inflammatory drugs: results of a collaborative meta-analysis. Br. Med. J. 312:1563-1566 (1996).Google Scholar
  5. 5.
    R. L. Savage, P. W. Moller, C. L. Ballantyne, and J. E. Wells. Variation in the risk of peptic ulcer complications with nonsteroidal antiinflammatory drug therapy. Arthritis Rheum. 36:84-90 (1993).Google Scholar
  6. 6.
    X. Le Loet. Safety of ketoprofen in the elderly: A prospective study on 20,000 patients. Scand. J. Rheumatol. Suppl. 83:21-27 (1989).Google Scholar
  7. 7.
    H. A. Wynne and M. Campbell. Pharmacoeconomics of nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmacoeconomics 3:107-123 (1993).Google Scholar
  8. 8.
    D. N. Bateman and J. G. Kennedy. Non-steroidal antiinflammatory drugs and elderly patients. Br. Med. J. 310:817-818 (1995).Google Scholar
  9. 9.
    R. A. Moore, M. R. Tramer, D. Carroll, P. J. Wiffen, and H. J. McQuay. Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs. Br. Med. J. 316:333-338 (1998).Google Scholar
  10. 10.
    H. J. McQuay, R. A. Moore, C. Eccleston, S. Morley, and A. C. Williams. Systematic review of outpatient services for chronic pain control. Health Technol. Assess. 1:1-135 (1997).Google Scholar
  11. 11.
    I. Tegeder, U. Muth-Selbach, J. Lotsch, G. Rusing, R. Oelkers, K. Brune, S. Meller, G. R. Kelm, F. Sorgel, and G. Geisslinger. Application of microdialysis for the determination of muscle and subcutaneous tissue concentrations after oral and topical ibuprofen administration. Clin. Pharmacol. Ther. 65:357-368 (1999).Google Scholar
  12. 12.
    M. Muller, H. Mascher, C. Kikuta, S. Schafer, M. Brunner, G. Dorner, and H. G. Eichler. Diclofenac concentrations in defined tissue layers after topical administration. Clin. Pharmacol. Ther. 62:293-299 (1997).Google Scholar
  13. 13.
    P. Lonnroth, P. A. Jansson, B. B. Fredholm, and U. Smith. Microdialysis of intercellular adenosine concentration in subcutaneous tissue in humans. Am. J. Physiol. 256:E250-255 (1989).Google Scholar
  14. 14.
    H. Lorentzen, F. Kallehave, H. J. Kolmos, U. Knigge, J. Bulow, and F. Gottrup. Gentamicin concentrations in human subcutaneous tissue. Antimicrob. Agents Chemother. 40:1785-1789 (1996).Google Scholar
  15. 15.
    P. Lonnroth and L. Strindberg. Validation of the “internal reference technique” for calibrating microdialysis catheters in situ. Acta Physiol. Scand. 153:375-380 (1995).Google Scholar
  16. 16.
    G. Geisslinger, S. Menzel, K. Wissel, and K. Brune. Pharmacokinetics of ketoprofen enantiomers after different doses of the racemate. Br. J. Clin. Pharmacol. 40:73-75 (1995).Google Scholar
  17. 17.
    M. Muller, B. Rohde, A. Kovar, A. Georgopoulos, H. G. Eichler, and H. Derendorf. Relationship between serum and free interstitial concentrations of cefodizime and cefpirome in muscle and subcutaneous adipose tissue of healthy volunteers measured by microdialysis. J. Clin. Pharmacol. 37:1108-1113 (1997).Google Scholar
  18. 18.
    A. Carabaza, F. Cabre, E. Rotllan, M. Gomez, M. Gutierrez, M. L. Garcia, and D. Mauleon. Stereoselective inhibition of inducible cyclooxygenase by chiral nonsteroidal antiinflammatory drugs. J. Clin. Pharmacol. 36:505-512 (1996).Google Scholar
  19. 19.
    A. Carabaza, F. Cabre, A. M. Garcia, E. Rotllan, M. L. Garcia, and D. Mauleon. Stereoselective inhibition of rat brain cyclooxygenase by dexketoprofen. Chirality 9:281-285 (1997).Google Scholar
  20. 20.
    K. Tobetto, Y. Yamamoto, M. Kataoka, T. Ando, K. Sugimoto, and M. Himeno. The effects of a newly developed nonsteroidal anti-inflammatory drug (M-5011) on arachidonic acid metabolism in rheumatoid synovial fibroblasts. Jpn. J. Pharmacol. 75: 371-379 (1997).Google Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Irmgard Tegeder
    • 1
  • Jörn Lötsch
    • 1
  • Martina Kinzig-Schippers
    • 2
  • Fritz Sörgel
    • 2
  • Gary R. Kelm
    • 3
  • Stephen T. Meller
    • 3
  • Gerd Geisslinger
    • 1
  1. 1.Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität FrankfurtFrankfurt am MainGermany
  2. 2.Institut für Biomedizinische und Pharmazeutische ForschungNürnberg-HeroldsbergGermany
  3. 3.Personal Health CareProcter & Gamble Health Care Research CenterMason

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