Skip to main content
SpringerLink
Log in

Preclinical Pharmacodynamics of Anti-Inflammatory Drugs

  • Chapter
Integration of Pharmacokinetics, Pharmacodynamics, and Toxicokinetics in Rational Drug Development

  • 298 Accesses

Abstract

During the past three decades research into the development of anti-inflammatory (AI) drugs has given rise in the main to the cyclooxygenase inhibitors. More recent efforts, based on a better understanding of the pathophysiology of the inflammatory process, have led to the development of unique and novel molecular entities as potential candidates for use in the treatment of inflammation. However, lack of suitable animal models that mimic the human disease and specific markers to follow immunological response that might possibly be associated with the disease process have made the selection of which new drug to take into clinical trials more difficult. This review discusses some of the advantages and disadvantages of animal models used routinely for the evaluation of AI agents and includes some suggestions as to how one might approach the development of newer models that may help identify novel AI drugs with varying mechanisms of therapeutic action.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Arthritis Foundation (1985). History of Rheumatology in the United States., pp. 115–142.

    Google Scholar 

  • Barden, J. A., and J. L. Deeker (1971). Mycoplasma hyorhinis swine arthritis. 1. clinical and microbiological features. Arth. Rheum.14, 193–201

    CAS  Google Scholar 

  • Billingham, M. E. J. (1990). Models of arthritis and the search for antiarthritic drugs. In M. L. E.Orme (Ed.), Anti-rheumatic Drugs Pergamon Press, New York. pp.1–47.

    Google Scholar 

  • Biotard, C. (1990). Pathophysiology of the autoimmune diseases. Klin. Wochenschr 68, 1–9.

    Google Scholar 

  • Brune, K., P. Graf, and M. Glatt (1976). Inhibition of prostaglandin synthesis in vivo by nonsteroidal anti-inflammatory drugs: evidence for the importance of pharmacokinet ics. Agents and Actions 6, 159–164.

    Article  PubMed  CAS  Google Scholar 

  • Campbell, I. L., and L. C. Harrison (1990). Molecular pathology of type I diabetes. Mol. Biol. 2, 299–309.

    Google Scholar 

  • Cannon, W. B., and J.E. Uridil (1921). Studies on the condition of activity in endocrine glands. VIII. Some effects on the denervated heart of stimulating the nerves of the liver. Am. J. Physiol. 58, 353–354.

    Google Scholar 

  • Caufield, J. P., A. Hein, R. Dynesius-Trentham, and D. Trentham (1982). Morphologic demonstration of two stages in the development of type II collagen-induced arthritis. Lab. Invest. 46, 321–343.

    Google Scholar 

  • Chritadoss, P., C. S. David, M. Shenoy, and S. Keve (1990). Alpha transgene in B10 mice suppresses the development of myasthenia gravis. Immunogenetics 31, 241–244.

    Google Scholar 

  • Cole, B. C. and G. H. Cassell (1979). Mycoplasma infections as models of chronic joint inflammation. Arth. Rheum. 22, 1375–1381.

    Article  CAS  Google Scholar 

  • Dinarello, C. A. (1984). Interleukin-1., Rev. Infec. Dis. 6, 51–95.

    Article  CAS  Google Scholar 

  • Dustin, M. L., R. Rothlein, A. K. Bhan, C. A. Dinarello, and T. A. Springer (1986). Induction by IL-1 and interferon-gamma: Tissue distribution, biochemistry, and function of natural adherence molecule (ICAM-1). J. Immunol. 137, 245–254.

    Google Scholar 

  • Folkman, J., and M. Klagsbrum (1987). Angiogenic factors. Science, 235 442–447.

    Article  PubMed  CAS  Google Scholar 

  • Friedman, S. M., D. N. Posnett, J. R. Tumang, B. C. Cole, and M. K. Crow (1991). A potential role for microbial superantigens in the pathogenesis of systemic autoimmune disease. Arth. Rheum. 34, 468–480.

    Article  CAS  Google Scholar 

  • Gilbertsen, R. B., and J. C. Sircar (1990). Enzyme cascades: Purine metabolism and immunosuppression. In C. Hansch (Ed.), Comprehensive Medicinal Chemistry Vol. 2, Pergamon Press, New York. pp. 443–480.

    Google Scholar 

  • Halliwell, B., J. R. Hoult, and D. R. Blake (1988) Oxidants, inflammation, and anti-inflammatory drugs. FASEB J., 2, 2867–2873.

    CAS  Google Scholar 

  • Hamberg, M., J. Svensson, and B. Samuelsson (1975). Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc. Natl. Acad. Sci. 72, 2994–2998.

    Google Scholar 

  • Hench, P. S., E. C. Kendall, C. H. Slocumb, and H. F. Polley (1949). Effect of a hormone of the adrenal cortex (17 hydroxy-11 dehydrocorticosterone), compound E and of pituitary adrenocortico-tropic hormone on rheumatoid arthritis: Preliminary report. Proc. Staff Meet. Mayo Clin. 24, 181.

    Google Scholar 

  • Lieberman, R., M. Katzper, M.Cooper, C. Myers, G. Burke, L. Sanathanan, and C. Peck (1991). Bayesian PK concentration controlled trials of suram in anticancer therapy. Clin. Pharmacol. Ther. 49, 155.

    Google Scholar 

  • Loewi, O., and E. Navratil (1926). Uber humorale Ubertragbarkeit der Herznervenwirkung. X. Mitteilung Uber das Schicksal des Vagusstoff. Pflugers Arch. Gesamte Physiol., 214 678–688.

    Article  CAS  Google Scholar 

  • Marry, P., M. Grootveld, and D.R. Blake (1990). Free radicals and hypoxic reperfusion injury. A mechanism producing persistent synovitis. Topical Reviews Arthritis Rheumatism Council, London.

    Google Scholar 

  • Martin, D. A., and E. W. Gelfand (1981). Biochemistry of diseases of immunodevelopment. Ann. Rev. Biochem. 50, 845–877.

    Google Scholar 

  • Mizel, S. B. (1989). The interleukins. FASEB.J. 3, 2379–2388.

    CAS  Google Scholar 

  • Needleman, P., M. Minkes, and A. Raz (1976). Thromboxanes: Selective biosynthesis and distinct biological properties. Science, 193 163–165.

    Google Scholar 

  • Nickerson, C. L., K. L. Hogen, H. S. Luthra, and C. S. David (1990). Effect of H-2 genes on expression of HLA-B27 and Yersinia-induced arthritis. Scan. J. Rheum. Suppl. 87, 85–90.

    Article  CAS  Google Scholar 

  • Otterness, I. G., and D. J. Gans (1988). Nonsteroidal anti-inflammatory drugs: an analysis of the relationship between laboratory animal and clinical doses, including species scaling. J. Pharm. Sci. 77, 790–794.

    Google Scholar 

  • Phillips, P. E. (1986). Infectious agents in the pathogenesis of rheumatoid arthritis. Seminars in Arth. Rheum. 16, 1–10.

    Google Scholar 

  • Popovic, S., and R. R. Barlett (1986). Disease modifying activity of HWA 486 on the development of SLE in MRL/1-mice. Agents and Actions 12, 313–314.

    Article  Google Scholar 

  • Rainsford, K. D. (1982). Adjuvant polyarthritis in rats: Is this a satisfactory model for screening antiarthritic drugs? Agents and Actions 12, 452–458.

    CAS  Google Scholar 

  • Rordorf-Adam, C., B. Rordorf, D. Serban, and A. Pataki (1986): The effects of anti-inflammatory agents on the serology and arthritis of the MRL 1pr/lpr mouse. Agents and Actions 19, 309–310.

    CAS  Google Scholar 

  • Samuelsson, B. (1983). Leukotrienes: Hypersensitivity reactions and inflammation. Science 220, 568–575.

    CAS  Google Scholar 

  • Shinagawa, H. (1990). The effects of HLA class II genes on the susceptability to autoimmune thyroid diseases. Fukuoka Igaku Zasshi. Fukuoka Acta Medica 97–111.

    Google Scholar 

  • Sircar, J. C., and R. B. Gilbertsen (1988). Purine nucleoside phosphorylase (PNP) inhibitors: Potentially selective immunosuppressive agents. Drugs of the Future 13, 653–668.

    Google Scholar 

  • Springer, T. A., M. A. Dustin, T. K. Kishimoto, and S. D. Marlin (1987). The lymphocyte function-associated LFA-1, CD 2, and LFA-3 molecules: Cell adhesion receptors of the immune system. Ann. Rev. Immunol. 5, 223–252.

    Google Scholar 

  • Stuart, J. M., A. S. Townes and A. H. Kang (1982). The role of collagen autoimmunity in animal models and human disease. J. Invest. Derm. 79, 121S- 127S.

    Google Scholar 

  • Taurog, J. D., J. P. Durand, F. A. el-Zaatari, and R. E. Hammer (1988). Studies of HLA-B27 associated disease. Am. J. Med. 85, 59–60.

    Google Scholar 

  • Trentham, D. E., A. S. Townes, and A. H. Kang (1977). Autoimmunity to type II collagen: an experimental model of arthritis. J. Expt. Med., 146 857–868.

    Article  CAS  Google Scholar 

  • van Arman, C. G., R. P. Carlson, E. A. Risley, R. H. Thomas, and G. W. Nuss (1970). Inhibitory effects of indomethacin, aspirin and certain other drugs on inflammation induced in rat and dog by carrageenin, sodium urate and ellagic acid. J. Pharmacol. Exp. Ther., 175 459–468.

    PubMed  Google Scholar 

  • Vane, J. R. (1971). Inhibition of prostaglandin synthesis as a mechanism of action for aspirin like drugs. Nature (New Biol.), 231 232–235.

    CAS  Google Scholar 

  • Winter, C. A., E. A. Risley, and C. W. Nuss (1962). Carrageenin induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proc. Soc. Expt. Biol. Med., 111 544–547.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Md, 20857, USA

    Asoke Mukherjee, Conrad Chen, Lucy Jean & Claude B. Coutinho

Authors
  1. Asoke Mukherjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Conrad Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucy Jean
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claude B. Coutinho
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Pharmacodynamics Research, American Cyanamid Company, Medical Research, Pearl River, New York, USA

    Avraham Yacobi Ph.D. (Director) (Director)

  2. Office of Research Resources, Center for Drug Evaluation and Research, Food and Drug Administration, Washington, D.C., USA

    Jerome P. Skelly Ph.D. (Deputy Director) (Deputy Director)

  3. Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA

    Vinod P. Shah Ph.D. (Acting Deputy Associate Director for Science) (Acting Deputy Associate Director for Science)

  4. Department of Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, California, USA

    Leslie Z. Benet Ph.D., Pharm.D.(Hon.) (Professor and Chairman) (Professor and Chairman)

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer Science+Business Media New York

About this chapter

Cite this chapter

Mukherjee, A., Chen, C., Jean, L., Coutinho, C.B. (1993). Preclinical Pharmacodynamics of Anti-Inflammatory Drugs. In: Yacobi, A., Skelly, J.P., Shah, V.P., Benet, L.Z. (eds) Integration of Pharmacokinetics, Pharmacodynamics, and Toxicokinetics in Rational Drug Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1520-0_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-1520-0_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-1522-4

  • Online ISBN: 978-1-4757-1520-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation