The Immunopharmacokinetics of Prednisone/Prednisolone

  • Leslie Z. Benet
  • Udo F. Legler
  • Brigitte M. Frey
  • Felix J. Frey
  • Sue Y. Tsang


Although immunosuppressive agents have been utilized extensively in a number of patient populations, little pharmacokinetic information has been available concerning the absorption and distribution of these compounds, and even less information has been available relating the efficacy and toxicity of these drugs to pharmacokinetic measurements. Studies in this area may be subsumed under the title immunopharmacokinetics which may be defined as the study of the rate processes of absorption, distribution, metabolism and excretion of immunoregulating (immunosuppressive and immunostimulating) drugs and their corresponding immunologic efficacious or toxic responses (1). Studies in our laboratory over the past few years have concentrated on defining the immunopharmacokinetics of prednisone and prednisolone, the most commonly used immunosuppressive agents. Before attempting to relate the kinetics of these exogenous glucocorticoids to their immunosuppressive effects, we felt that it was necessary to accurately define the pharmacokinetics of these agents in both normal volunteers and the patient populations receiving the drug.


Immunosuppressive Activity Mixed Lymphocyte Reaction Apparent Clearance Exogenous Glucocorticoid Tritiated Thymidine Incorporation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    L.Z. Benet, B.M. Frey, T.L. Ding and F.J. Frey, The pharmacokinetics of immunoregulating drugs: Immunopharmacokinetics, in: “Advances in Immunopharmacology” J. Hadden, L. Chedid, P. Mullen and F. Spreafico, eds., Pergamon Press, Oxford (1981), pp. 29–36.Google Scholar
  2. 2.
    F.J. Frey, B.M. Frey and L.Z. Benet, Liquid-chromatographic measurement of endogenous and exogenous glucocorticoids in plasma, Clin. Chem. 25: 1944–1947 (1979).PubMedGoogle Scholar
  3. 3.
    H.L. Behm and J.G. Wagner, Errors in interpretation of data from equilibrium dialysis protein binding experiments, Res. Commun. Chem. Path. Pharmacol. 26: 145–160 (1979).Google Scholar
  4. 4.
    T.N. Tozer, J.G. Gambertoglio, D.E. Furst, D. Avery and N.H.G. Holford, Volume shifts during equilibrium dialysis and protein binding estimates - application to prednisolone binding in man, J. Pharm. Sci. 72: 1442–1446 (1983).PubMedCrossRefGoogle Scholar
  5. 5.
    M.E. Pickup, Clinical pharmacokinetics of prednisone and prednisolone, Clin. Pharmacokin. 4: 111–128 (1979).CrossRefGoogle Scholar
  6. 6.
    J.G. Gambertoglio, W.J.C. Amend and L.Z. Benet, Pharmacokinetics and bioavailability of prednisone and prednisolone in healthy volunteers and patients: A review, J. Pharmacokin. Biopharm. 8: 1–52 (1980).CrossRefGoogle Scholar
  7. 7.
    A.W. Meikle, J.A. Weed and F.H. Tyler, Kinetics and intercon- version of prednisolone and prednisone studied with new radioimmunoassays, J. Clin. Endocrinol. Metab. 41: 717–721 (1975).PubMedCrossRefGoogle Scholar
  8. 8.
    M.E. Pickup, J.R. Lowe, P.A. Leathan, V.M. Rhind, V. Wright and W.W. Downie, Dose-dependent pharmacokinetics of prednisone and prednisolone, Eur. J. Clin. Pharmacol. 12: 213–219 (1977).PubMedCrossRefGoogle Scholar
  9. 9.
    J.C.K. Loo, I.J. McGilveray, N. Jordan, J. Moffatt and R. Brien, Dose-dependent pharmacokinetics of prednisone and prednisolone in man, J. Pharm. Pharmacol. 30: 736 (1978).PubMedCrossRefGoogle Scholar
  10. 10.
    A. Tanner, F. Bochner, J. Caff in, J. Halliday and L. Powell, Dose-dependent prednisolone kinetics, Clin. Pharmacol. Ther. 25: 571–578 (1979).PubMedGoogle Scholar
  11. 11.
    S. Al-Habet and H.L. Rogers, Pharmacokinetics of intravenous and oral prednisolone, Br. J. Clin. Pharmacol. 10: 503–508 (1980).PubMedGoogle Scholar
  12. 12.
    F.J. Frey, B.M. Frey, A. Greither and L.Z. Benet, Prednisolone clearance at steady state in dogs, J. Pharmacol. Exp. Ther. 215: 287–291 (1980).PubMedGoogle Scholar
  13. 13.
    U.F. Legler, F.J. Frey and L.Z. Benet, Prednisolone clearance at steady state in man, J. Clin. Endocrinol. Metab. 55: 762–767 (1982).PubMedCrossRefGoogle Scholar
  14. 14.
    I.H. Mill, H.P. Schedl, P.S. Chen and F.C. Bartter, The effect of estrogen administration on the metabolism and protein binding of hydrocortisone, J. Clin. Endocrinol. Metab. 20: 515–528 (1960).CrossRefGoogle Scholar
  15. 15.
    U.F. Legler and L.Z. Benet, Marked alteration in prednisolone kinetics in women taking oral-contraceptive steroids, Clin. Pharmacol. Ther. 31: 243 (1982).Google Scholar
  16. 16.
    P.R. Ortiz de Montellano, K.L. Kunze, G.S. Yost and B.A. Mico, Self-catalyzed destruction of cytochrome P-450: Covalent binding of ethynyl sterols to prosthetic heme, Proc. Natl. Acad. Sci. 76: 746–749 (1979).PubMedCrossRefGoogle Scholar
  17. 17.
    P.R. Ortiz de Montellano and K.L. Kunze, Self-catalyzed inac- tivation of hepatic cytochrome P-450 by ethynyl substrates, J. Biol. Chem. 255: 5578–5585 (1980).PubMedGoogle Scholar
  18. 18.
    M. Kozower, L. Veatch and M.M. Kaplan, Decreased clearance of prednisolone, a factor in the development of corticosteroid side effects, J. Clin. Endocrinol. Metab. 38: 407–412 (1974).PubMedCrossRefGoogle Scholar
  19. 19.
    J. Gambertoglio, F. Vincenti, N. Feduska, J. Birnbaum, 0. Salvatierra and W. Amend, Prednisolone disposition in cush- ingoid and noncushingoid kidney transplant patients, J. Clin. Endocrinol. Metab. 51: 561–565 (1980).PubMedCrossRefGoogle Scholar
  20. 20.
    F.J. Frey, W.J.C. Amend, F. Lozada, B.M. Frey, N.H.G. Holford and L.Z. Benet, Pharmacokinetics of prednisolone and endogenous hydrocortisone levels in cushingoid and non-cushingoid patients, Eur. J. Clin. Pharmacol. 21: 235–242 (1981).PubMedCrossRefGoogle Scholar
  21. 21.
    F.J. Frey, W.J.C. Amend, Jr., F. Lozada, B.M. Frey and L.Z. Benet, Endogenous hydrocortisone, a possible factor contributing to the genesis of cushingoid habitus in patients on prednisone, J. Clin. Endocrinol. Metab. 53: 1076–1080 (1981).PubMedCrossRefGoogle Scholar
  22. 22.
    A.S. Fauci, D.C. Dale and J.E. Barlow, Glucocorticosteroid therapy: Mechanisms of action of steroid hormones, Ann. Intern. Med. 84: 304–315 (1976).PubMedGoogle Scholar
  23. 23.
    A.S. Fauci, Mechanisms of the immunosuppressive and antiinflammatory effects of glucocorticoids, J. Immunopharmacol. 1:1–25 (1978-79).PubMedGoogle Scholar
  24. 24.
    D.N. Ilfeld, R.S. Krakauer and R.M. Blaese, Suppression of the human autologous mixed lymphocyte reaction by physiologic concentrations of hydrocortisone, J. Immunol. 119: 428–434 (1977).PubMedGoogle Scholar
  25. 25.
    J.F. Bach, “The Mode of Action of Immunosuppressive Agents,” North Holland, Amsterdam (1975).Google Scholar
  26. 26.
    K.C. Cochrum, O. Salvatierra, Jr., H.A. Perkins and F.O. Belzer, MLC testing in renal transplantation, Transplant. Proc. 7: 659–662 (1975).Google Scholar
  27. 27.
    A. Laborde and J.-F. Bach, Immunologie-inhibition et stimulation par 1’incorporation de thymidine par les lymphocytes en culture mixte, C.R. Acad. Sci., Paris, D. 272: 509–512 (1971).Google Scholar
  28. 28.
    J-F. Bach, M. Dardenne and M.-A. Bach, Dosage des metabolites actifs des immunosuppresseurs dans le serum, La Nouvelle Presse Medicale 1: 2293–2298 (1972).PubMedGoogle Scholar
  29. 29.
    B.M. Frey, F.J. Frey, L.Z. Benet and K.C. Cochrum, Modification of the mixed lymphocyte reaction for pharmacokinetic assessment of immunosuppressive activity in human plasma, Int. J. Immunopharmac. 2: 129–134 (1980).CrossRefGoogle Scholar
  30. 30.
    B.M. Frey, F.J. Frey, K.C. Cochrum and L.Z. Benet, Induction kinetics of human suppressor cells in the mixed lymphocyte reaction and influence of prednisolone on their genesis, Cellular Immunol. 56: 225–234 (1980).CrossRefGoogle Scholar
  31. 31.
    B.M. Frey, F.J. Frey, N.H.G. Holford, F. Lozada and L.Z. Benet, Prednisolone pharmacodynamics assessed by inhibition of the mixed lymphocyte reaction, Transplantation 33: 578–584 (1982).PubMedCrossRefGoogle Scholar
  32. 32.
    S.Y. Tsang, B.M. Frey and L.Z. Benet, Effects of corticosteroids on thein vitroproliferative response of human lymphocytes to allogeneic cells, Abstracts of APhA Academy of Pharmaceutical Sciences 11 (2): 143 (1981).Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Leslie Z. Benet
    • 1
  • Udo F. Legler
    • 1
  • Brigitte M. Frey
    • 1
  • Felix J. Frey
    • 1
  • Sue Y. Tsang
    • 1
  1. 1.Department of Pharmacy, School of PharmacyUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations