Skip to main content
Log in

A comparison of synovial fluid concentrations of non-steroidal anti-inflammatory drugs with theirin vitro activity

  • Inflammation and Immunomodulation
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

For NSAIDs it has been widely accepted that prostaglandin inhibition is their mechanism of action in clinical use. Yet many other actions have been described, although it is unclear to what extent these may contribute to clinical activity. This review attempts to relate some of the experimental activities of NSAIDs to concentrations of drugs which occur in clinical use. Since it is assumed that to be effective a drug must reach its target site of action, synovial fluid concentrations for NSAIDs are considered. The resulting analysis suggests that prostaglandin inhibition is a viable mode of action for most, if not all, NSAIDs. However, some NSAIDS may rely as much, if not more, on other actions for their anti-inflammatory effect.

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

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. W. J. Wallis and P. A. Simkin,Antirheumatic drug concentrations in human synovial fluid tissue. Clin. Pharmacokin.8, 496–522 (1983).

    Google Scholar 

  2. H. Spahn, K. Thabe, E. Mutschler, K. Tillmann and I. Gikalov,Concentration of azapropazone in synovial tissues and fluid Eur. J. Clin. Pharmacol.32, 303–307 (1987).

    Article  PubMed  Google Scholar 

  3. S. Wanwimolruk, P. M. Brooks and D. J. Birkett,Protein binding of non-steroidal anti-inflammatory drugs in plasma and synovial fluid of arthritic patients. Br. J. Clin. Pharmacol.15, 91–94 (1983).

    PubMed  Google Scholar 

  4. K. Brune, K. D. Rainsford, K. Wagner and B. A. Peskar,Inhibition by anti-inflammatory drugs of prostaglandin production in cultured macrophages. Naunyn-Schmiedeberg's Arch. Pharmacol.315, 269–276 (1981).

    Article  Google Scholar 

  5. S. Rashad, P. Revell, A. Hemingway, F. Low, K. D. Rainsford and F. Walker,Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis. The Lancet, 2nd September, 519–522 (1989).

  6. E. Seppala, M. Nissila, H. Isomaki, P, Nuotio, E. Nykanen, O. Laitinen and H. Vapaatalo,Comparison of the effects of different anti-inflammatory drugs of synovial fluid prostanoid concentrations in patients with rheumatoid arthritis. Clin. Rheumatol.4, 315–320 (1985).

    PubMed  Google Scholar 

  7. D. C. Brater,Drug-drug and drug-disease interactions with non-steroidal anti-inflammatory drugs. Am. J. Med.80, 62–77 (1986).

    Google Scholar 

  8. K. D. Rainsford, A. Davies, L. Mundy and I. Ginsburg,Comparative effects of azapropazone on cellular events at inflamed sites. Influence on joint pathology in arthritic rats, leucocyte superoxide and eicosanoid production, platelet aggregation, synthesis of cartilage proteoglycans, synovial production and actions of interleukin-1 in cartilage resorption correlated with drug uptake into cartilage in vitro. J. Pharm. Pharmacol.41, 322–330 (1989).

    PubMed  Google Scholar 

  9. F. Silvieri, A. Allegrezzo Guilietti, S. Muti and G. Piergiacomi,Chemiluminescence of polymorphonuclear leucocytes and non-steroidal anti-inflammatory agents. Clin. Trials. J.25, 390–400 (1988).

    Google Scholar 

  10. P. D. Fowler, M. F. Shadforth, P. R. Crook and V. A. John,Plasma and synovial fluid concentrations of diclofenac sodium and its major hydroxylated metabolites during long-term treatment of rheumatoid arthritis. Eur. J. Clin. Pharmacol.25, 389–394 (1983).

    Article  PubMed  Google Scholar 

  11. T. M. Chalmers, R. C. Glass and P. C. Risdall,Concentrations of flurbiprofen in serum and synovial fluid from patients with active rheumatoid disease: some preliminary observations. Curr. Med. Res. Opin.5, 17–20 (1977).

    PubMed  Google Scholar 

  12. R. C. Glass and A. J. Swannell,Concentrations of ibuprofen in serum and synovial fluid from patients with arthritis. Brit. J. Clin. Pharmacol.6, 453P-454P (1978).

    Google Scholar 

  13. H. W. Emori, G. D. Champion, R. Bluestone and H. E. Paulus,Simultaneous pharmacokinetics of indomethacin in serum and synovial fluid. Ann. Rheum. Dis.32, 433–435 (1973).

    PubMed  Google Scholar 

  14. W. S. Mitchell, P. Scott, A. C. Kennedy, P. M. Brooks, R. Templeton and M. G. Jefferies,Clinico-pharmacological studies on ketoprofen (‘Orudis’). Curr. Med. Res. Opin.3, 423–430 (1975).

    Google Scholar 

  15. S. Jalava, A. Saarimaa, M. Anttila and H. Sundquist,Naproxen concentrations in serum, synovial fluid and synovium. Scand. J. Rheumatol.6, 155–157 (1977).

    PubMed  Google Scholar 

  16. R. K. Verbeeck, C. J. Richardson and K. L. N. Blocka,Clinical pharmacokinetics of piroxicam. J. Rheumatol.13, 789–796 (1986).

    PubMed  Google Scholar 

  17. S. H. Dromgoole, D. E. Furst, R. K. Desiraju, R. K. Nayak, M. A. Kirschenbaum and H. E. Paulus,Tolmetin kinetics and synovial fluid prostaglandin E levels in rheumatoid arthritis. Clin. Pharmacol. Ther.32, 371–377 (1982).

    PubMed  Google Scholar 

  18. J. O. Minta and M. D. Williams,Some nonsteroidal antiinflammatory drugs inhibit the generation of superoxide anions by activated polymorphs by blocking ligand-receptor interactions. J. Rheumatol.12, 751–757 (1975).

    Google Scholar 

  19. C. Friman, C. Johnston, C. Chew and P. Davies,Effect of diclofenac sodium, tolfenamic acid and indomethacin on the production of superoxide induced by n-formyl-methionylleucyl-phenylalanine in normal human polymorphonuclear leukocytes. Scand. J. Rheumatol.15, 41–46 (1986).

    PubMed  Google Scholar 

  20. K. D. Rainsford,Effects of anti-inflammatory drugs on the release from porcine synovial tissue in vitro of interleukin 1 like cartilage degrading activity. Agents and Actions21, 337–340 (1987).

    Article  PubMed  Google Scholar 

  21. K. G. Couchman and H. Sheppeard,The effect of antirheumatic drugs on factors from porcine synovium inducing chondrocyte mediated cartilage degradation. Agents and Actions19, 116–122 (1986).

    Article  PubMed  Google Scholar 

  22. D. A. Lewis, R. B. Capstick and R. J. Ancill,The action of azapropazone, oxyphenbutazone and phenylbutazone on lysosomes. J. Pharm. Pharmacol.23, 931–935 (1971).

    PubMed  Google Scholar 

  23. P. A. Todd and E. M. Sorkin,Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs35, 244–285 (1988).

    PubMed  Google Scholar 

  24. R. J. Smith, C. Sabin, H. Gilchrest and S. Williams,Effect of anti-inflammatory drugs on lysosomes and lysosomal enzymes from rat liver. Biochem. Pharmacol.25, 2171–2177 (1976).

    Article  PubMed  Google Scholar 

  25. R. J. Flower and J. R. Vane,Inhibition of prostaglandin biosynthesis. Biochem. Pharmacol.23, 1439–1450 (1974).

    Article  PubMed  Google Scholar 

  26. J. Migne, Y. Vedrine, G. Bourat, J. Fournel and D. Heusse,Action of ketoprofen on hepatic lysosome in the rat. Rheumatol. Rehabil. Supplement 15–19 (1976).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Urquhart, E. A comparison of synovial fluid concentrations of non-steroidal anti-inflammatory drugs with theirin vitro activity. Agents and Actions 32, 261–265 (1991). https://doi.org/10.1007/BF01980883

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01980883

Keywords

Navigation