Clinical Pharmacokinetics

, Volume 44, Issue 1, pp 61–98 | Cite as

Pharmacokinetics and Pharmacodynamics of Systemically Administered Glucocorticoids

  • David Czock
  • Frieder KellerEmail author
  • Franz Maximilian Rasche
  • Ulla Häussler
Review Article


Glucocorticoids have pleiotropic effects that are used to treat diverse diseases such as asthma, rheumatoid arthritis, systemic lupus erythematosus and acute kidney transplant rejection. The most commonly used systemic glucocorticoids are hydrocortisone, prednisolone, methylprednisolone and dexamethasone. These glucocorticoids have good oral bioavailability and are eliminated mainly by hepatic metabolism and renal excretion of the metabolites. Plasma concentrations follow a biexponential pattern. Two-compartment models are used after intravenous administration, but one-compartment models are sufficient after oral administration.

The effects of glucocorticoids are mediated by genomic and possibly nongenomic mechanisms. Genomic mechanisms include activation of the cytosolic glucocorticoid receptor that leads to activation or repression of protein synthesis, including cytokines, chemokines, inflammatory enzymes and adhesion molecules. Thus, inflammation and immune response mechanisms may be modified. Nongenomic mechanisms might play an additional role in glucocorticoid pulse therapy.

Clinical efficacy depends on glucocorticoid pharmacokinetics and pharmacodynamics. Pharmacokinetic parameters such as the elimination half-life, and pharmacodynamic parameters such as the concentration producing the half-maximal effect, determine the duration and intensity of glucocorticoid effects. The special contribution of either of these can be distinguished with pharmacokinetic/pharmacodynamic analysis. We performed simulations with a pharmacokinetic/pharmacodynamic model using T helper cell counts and endogenous Cortisol as biomarkers for the effects of methylprednisolone. These simulations suggest that the clinical efficacy of low-dose glucocorticoid regimens might be increased with twice-daily glucocorticoid administration.


Glucocorticoid Prednisolone Methylprednisolone Glucocorticoid Receptor Diffuse Alveolar Haemorrhage 
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.



This study was supported by the European Commission within the PharmDIS project (BMH4-CT98-9548 and IST Craft-2001-52107). The authors have no conflicts of interest to disclose.


  1. 1.
    Mager DE, Wyska E, Jusko WJ. Diversity of mechanism-based pharmacodynamic models. Drug Metab Dispos 2003; 31(5): 510–8PubMedGoogle Scholar
  2. 2.
    Meibohm B, Derendorf H. Pharmacokinetic/pharmacodynamic studies in drug product development. J Pharm Sci 2002; 91(1): 18–31PubMedGoogle Scholar
  3. 3.
    Derendorf H, Hochhaus G, Mollmann H, et al. Receptor-based pharmacokinetic-pharmacodynamic analysis of corticosteroids. J Clin Pharmacol 1993; 33(2): 115–23PubMedGoogle Scholar
  4. 4.
    Holford NH, Sheiner LB. Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clin Pharmacokinet 1981; 6(6): 429–53PubMedGoogle Scholar
  5. 5.
    Mager DE, Jusko WJ. Quantitative structure-pharmacokinetic/pharmacodynamic relationships of corticosteroids in man. J Pharm Sci 2002; 91(11): 2441–51PubMedGoogle Scholar
  6. 6.
    Kong AN, Ludwig EA, Slaughter RL, et al. Pharmacokinetics and pharmacodynamic modeling of direct suppression effects of methylprednisolone on serum Cortisol and blood histamine in human subjects. Clin Pharmacol Ther 1989; 46(6): 616–28PubMedGoogle Scholar
  7. 7.
    Mollmann H, Rohdewald P, Barth J, et al. Pharmacokinetics and dose linearity testing of methylprednisolone phosphate. Biopharm Drug Dispos 1989; 10(5): 453–64PubMedGoogle Scholar
  8. 8.
    Mollmann H, Rohdewald P, Barth J, et al. Comparative pharmacokinetics of methylprednisolone phosphate and hemisuccinate in high doses. Pharm Res 1988; 5(8): 509–13PubMedGoogle Scholar
  9. 9.
    Derendorf H, Mollmann H, Barth J, et al. Pharmacokinetics and oral bioavailability of hydrocortisone. J Clin Pharmacol 1991; 31(5): 473–6PubMedGoogle Scholar
  10. 10.
    Kawai S, Ichikawa Y, Homma M. Differences in metabolic properties among Cortisol, prednisolone, and dexamethasone in liver and renal diseases: accelerated metabolism of dexamethasone in renal failure. J Clin Endocrinol Metab 1985; 60(5): 848–54PubMedGoogle Scholar
  11. 11.
    Hare LE, Yeh KC, Ditzler CA, et al. Bioavailability of dexamethasone. II: dexamethasone phosphate. Clin Pharmacol Ther 1975; 18(3): 330–7PubMedGoogle Scholar
  12. 12.
    Varis T, Rivisto KT, Backman JT, et al. The cytochrome P450 3A4 inhibitor itraconazole markedly increases the plasma concentrations of dexamethasone and enhances its adrenal-suppressant effect. Clin Pharmacol Ther 2000; 68(5): 487–94PubMedGoogle Scholar
  13. 13.
    Toth GG, Kloosterman C, Uges DR, et al. Pharmacokinetics of high-dose oral and intravenous dexamethasone. Ther Drug Monit 1999; 21(5): 532–5PubMedGoogle Scholar
  14. 14.
    Garg V, Jusko WJ. Bioavailability and reversible metabolism of prednisone and prednisolone in man. Biopharm Drug Dispos 1994; 15(2): 163–72PubMedGoogle Scholar
  15. 15.
    Patel PM, Selby PJ, Graham MA, et al. Pharmacokinetics of high dose methylprednisolone and use in hematological malignancies. Hematol Oncol 1993; 11(2): 89–96PubMedGoogle Scholar
  16. 16.
    Al-Habet SM, Rogers HJ. Methylprednisolone pharmacokinetics after intravenous and oral administration. Br J Clin Pharmacol 1989; 27(3): 285–90PubMedGoogle Scholar
  17. 17.
    Derendorf H, Mollmann H, Rohdewald P, et al. Kinetics of methylprednisolone and its hemisuccinate ester. Clin Pharmacol Ther 1985; 37(5): 502–7PubMedGoogle Scholar
  18. 18.
    Rose JQ, Yurchak AM, Jusko WJ. Dose dependent pharmacokinetics of prednisone and prednisolone in man. J Pharmacokinet Biopharm 1981; 9(4): 389–417PubMedGoogle Scholar
  19. 19.
    Tanner A, Bochner F, Caffin J, et al. Dose-dependent prednisolone kinetics. Clin Pharmacol Ther 1979; 25 (5 Pt 1): 571–8PubMedGoogle Scholar
  20. 20.
    Duggan DE, Yeh KC, Matalia N, et al. Bioavailability of oral dexamethasone. Clin Pharmacol Ther 1975; 18(2): 205–9PubMedGoogle Scholar
  21. 21.
    Rohatagi S, Hochhaus G, Mollmann H, et al. Pharmacokinetic interaction between endogenous Cortisol and exogenous corticosteroids. Pharmazie 1995; 50(9): 610–3PubMedGoogle Scholar
  22. 22.
    Rosman PM, Benn R, Kay M, et al. Cortisol binding in uremic plasma. I: absence of abnormal Cortisol binding to Cortisol binding to corticosteroid-binding globulin. Nephron 1984; 37(3): 160–5PubMedGoogle Scholar
  23. 23.
    Rosman PM, Benn R, Kay M, et al. Cortisol binding in uremic plasma. II: decreased Cortisol binding to albumin. Nephron 1984; 37(4): 229–31PubMedGoogle Scholar
  24. 24.
    Wald JA, Law RM, Ludwig EA, et al. Evaluation of doserelated pharmacokinetics and pharmacodynamics of prednisolone in man. J Pharmacokinet Biopharm 1992; 20(6): 567–89PubMedGoogle Scholar
  25. 25.
    Dunn TE, Ludwig EA, Slaughter RL, et al. Pharmacokinetics and pharmacodynamics of methylprednisolone in obesity. Clin Pharmacol Ther 1991; 49(5): 536–49PubMedGoogle Scholar
  26. 26.
    Ludwig EA, Slaughter RL, Savliwala M, et al. Steroid-specific effects of ketoconazole on corticosteroid disposition: unaltered prednisolone elimination. DICP 1989; 23(11): 858–61PubMedGoogle Scholar
  27. 27.
    Derendorf H, Rohdewald P, Mollmann H, et al. Pharmacokinetics of prednisolone after high doses of prednisolone hemisuccinate. Biopharm Drug Dispos 1985; 6(4): 423–32PubMedGoogle Scholar
  28. 28.
    Meno-Tetang GM, Blum RA, Schwartz KE, et al. Effects of oral prasterone (dehydroepiandrosterone) on single-dose pharmacokinetics of oral prednisone and Cortisol suppression in normal women. J Clin Pharmacol 2001; 41(11): 1195–205PubMedGoogle Scholar
  29. 29.
    Yamashita SK, Ludwig EA, Middleton Jr E, et al. Lack of pharmacokinetic and pharmacodynamic interactions between ketoconazole and prednisolone. Clin Pharmacol Ther 1991; 49(5): 558–70PubMedGoogle Scholar
  30. 30.
    Booker BM, Magee MH, Blum RA, et al. Pharmacokinetic and pharmacodynamic interactions between diltiazem and methylprednisolone in healthy volunteers. Clin Pharmacol Ther 2002; 72(4): 370–82PubMedGoogle Scholar
  31. 31.
    Chow FS, Sharma A, Jusko WJ. Modeling interactions between adrenal suppression and T-helper lymphocyte trafficking during multiple dosing of methylprednisolone. J Pharmacokinet Biopharm 1999; 27(6): 559–75PubMedGoogle Scholar
  32. 32.
    Barth J, Damoiseaux M, Mollmann H, et al. Pharmacokinetics and pharmacodynamics of prednisolone after intravenous and oral administration. Int J Clin Pharmacol Ther Toxicol 1992; 30(9): 317–24PubMedGoogle Scholar
  33. 33.
    Bergrem H. The influence of uremia on pharmacokinetics and protein binding of prednisolone. Acta Med Scand 1983; 213(5): 333–7PubMedGoogle Scholar
  34. 34.
    Boekenoogen SJ, Szefler SJ, Jusko WJ. Prednisolone disposition and protein binding in oral contraceptive users. J Clin Endocrinol Metab 1983; 56(4): 702–9PubMedGoogle Scholar
  35. 35.
    Rohatagi S, Barth J, Mollmann H, et al. Pharmacokinetics of methylprednisolone and prednisolone after single and multiple oral administration. J Clin Pharmacol 1997; 37(10): 916–25PubMedGoogle Scholar
  36. 36.
    Mollmann H, Hochhaus G, Rohatagi S, et al. Pharmacokinetic/pharmacodynamic evaluation of deflazacort in comparison to methylprednisolone and prednisolone. Pharm Res 1995; 12(7): 1096–100PubMedGoogle Scholar
  37. 37.
    Ebling WF, Milsap RL, Szefler SJ, et al. 6 α-methylprednisolone and 6 α-methylprednisone plasma protein binding in humans and rabbits. J Pharm Sci 1986; 75(8): 760–3PubMedGoogle Scholar
  38. 38.
    Szefler SJ, Ebling WF, Georgitis JW, et al. Methylprednisolone versus prednisolone pharmacokinetics in relation to dose in adults. Eur J Clin Pharmacol 1986; 30(3): 323–9PubMedGoogle Scholar
  39. 39.
    Szefler SJ, Rose JQ, Ellis EF, et al. The effect of troleandomycin on methylprednisolone elimination. J Allergy Clin Immunol 1980; 66(6): 447–51PubMedGoogle Scholar
  40. 40.
    Slayter KL, Ludwig EA, Lew KH, et al. Oral contraceptive effects on methylprednisolone pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 1996; 59(3): 312–21PubMedGoogle Scholar
  41. 41.
    Cummings DM, Larijani GE, Conner DP, et al. Characterization of dexamethasone binding in normal and uremic human serum. DICP 1990; 24(3): 229–31PubMedGoogle Scholar
  42. 42.
    Rohdewald P, Mollmann H, Barth J, et al. Pharmacokinetics of dexamethasone and its phosphate ester. Biopharm Drug Dispos 1987; 8(3): 205–12PubMedGoogle Scholar
  43. 43.
    Hochhaus G, Barth J, al-Fayoumi S, et al. Pharmacokinetics and pharmacodynamics of dexamethasone sodium-m-sulfobenzoate (DS) after intravenous and intramuscular administration: a comparison with dexamethasone phosphate (DP). J Clin Pharmacol 2001; 41(4): 425–34PubMedGoogle Scholar
  44. 44.
    Gupta SK, Ritchie JC, Ellinwood EH, et al. Modeling the pharmacokinetics and pharmacodynamics of dexamethasone in depressed patients. Eur J Clin Pharmacol 1992; 43(1): 51–5PubMedGoogle Scholar
  45. 45.
    Lee KH, Shin JG, Chong WS, et al. Time course of the changes in prednisolone pharmacokinetics after co-administration or discontinuation of rifampin. Eur J Clin Pharmacol 1993; 45(3): 287–9PubMedGoogle Scholar
  46. 46.
    Lebrun-Vignes B, Archer VC, Diquet B, et al. Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and Cortisol secretion in healthy subjects. Br J Clin Pharmacol 2001; 51(5): 443–50PubMedGoogle Scholar
  47. 47.
    Imani S, Jusko WJ, Steiner R. Diltiazem retards the metabolism of oral prednisone with effects on T-cell markers. Pediatr Transplant 1999; 3(2): 126–30PubMedGoogle Scholar
  48. 48.
    Kandrotas RJ, Slaughter RL, Brass C, et al. Ketoconazole effects on methylprednisolone disposition and their joint suppression of endogenous Cortisol. Clin Pharmacol Ther 1987; 42(4): 465–70PubMedGoogle Scholar
  49. 49.
    Glynn AM, Slaughter RL, Brass C, et al. Effects of ketoconazole on methylprednisolone pharmacokinetics and Cortisol secretion. Clin Pharmacol Ther 1986; 39(6): 654–9PubMedGoogle Scholar
  50. 50.
    Varis T, Backman JT, Rivisto KT, et al. Diltiazem and mibefradil increase the plasma concentrations and greatly enhance the adrenal-suppressant effect of oral methylprednisolone. Clin Pharmacol Ther 2000; 67(3): 215–21PubMedGoogle Scholar
  51. 51.
    Fost DA, Leung DY, Martin RJ, et al. Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy. J Allergy Clin Immunol 1999; 103(6): 1031–5PubMedGoogle Scholar
  52. 52.
    Varis T, Rivisto KT, Neuvonen PJ. Grapefruit juice can increase the plasma concentrations of oral methylprednisolone. Eur J Clin Pharmacol 2000; 56(6–7): 489–93PubMedGoogle Scholar
  53. 53.
    Seidegard J, Simonsson M, Edsbacker S. Effect of an oral contraceptive on the plasma levels of budesonide and prednisolone and the influence on plasma Cortisol. Clin Pharmacol Ther 2000; 67(4): 373–81PubMedGoogle Scholar
  54. 54.
    Tornatore KM, Morse GD, Jusko WJ, et al. Methylprednisolone disposition in renal transplant recipients receiving triple-drug immunosuppression. Transplantation 1989; 48(6): 962–5PubMedGoogle Scholar
  55. 55.
    Milad MA, Ludwig EA, Lew KH, et al. The pharmacokinetics and pharmacodynamics of methylprednisolone in chronic renal failure. Am J Ther 1994; 1(1): 49–57PubMedGoogle Scholar
  56. 56.
    Milsap RL, Plaisance KI, Jusko WJ. Prednisolone disposition in obese men. Clin Pharmacol Ther 1984; 36(6): 824–31PubMedGoogle Scholar
  57. 57.
    Wald JA, Jusko WJ. Corticosteroid pharmacodynamic modeling: osteocalcin suppression by prednisolone. Pharm Res 1992; 9(8): 1096–8PubMedGoogle Scholar
  58. 58.
    Mager DE, Lin SX, Blum RA, et al. Dose equivalency evaluation of major corticosteroids: pharmacokinetics and cell trafficking and Cortisol dynamics. J Clin Pharmacol 2003; 43(11): 1216–27PubMedGoogle Scholar
  59. 59.
    Meibohm B, Derendorf H, Mollmann H, et al. Mechanismbased PK/PD model for the lymphocytopenia induced by endogenous and exogenous corticosteroids. Int J Clin Pharmacol Ther 1999; 37(8): 367–76PubMedGoogle Scholar
  60. 60.
    Oosterhuis B, ten Berge IJ, Schellekens PT, et al. Prednisolone concentration-effect relations in humans and the influence of plasma hydrocortisone. J Pharmacol Exp Ther 1986; 239(3): 919–26PubMedGoogle Scholar
  61. 61.
    Magee MH, Blum RA, Lates CD, et al. Pharmacokinetic/pharmacodynamic model for prednisolone inhibition of whole blood lymphocyte proliferation. Br J Clin Pharmacol 2002; 53(5): 474–84PubMedGoogle Scholar
  62. 62.
    Chakraborty A, Blum RA, Cutler DL, et al. Pharmacoimmunodynamic interactions of interleukin-10 and prednisone in healthy volunteers. Clin Pharmacol Ther 1999; 65(3): 304–18PubMedGoogle Scholar
  63. 63.
    Reiss WG, Slaughter RL, Ludwig EA, et al. Steroid dose sparing: pharmacodynamic responses to single versus divided doses of methylprednisolone in man. J Allergy Clin Immunol 1990; 85(6): 1058–66PubMedGoogle Scholar
  64. 64.
    Uhl A, Czock D, Boehm BO, et al. Pharmacokinetics and pharmacodynamics of methylprednisolone after one bolus dose compared with two dose fractions. J Clin Pharm Ther 2002; 27(4): 281–7PubMedGoogle Scholar
  65. 65.
    Derendorf H, Mollmann H, Krieg M, et al. Pharmacodynamics of methylprednisolone phosphate after single intravenous administration to healthy volunteers. Pharm Res 1991; 8(2): 263–8PubMedGoogle Scholar
  66. 66.
    Braat MC, Oosterhuis B, Koopmans RP, et al. Kinetic-dynamic modeling of lymphocytopenia induced by the combined action of dexamethasone and hydrocortisone in humans, after inhalation and intravenous administration of dexamethasone. J Pharmacol Exp Ther 1992; 262(2): 509–15PubMedGoogle Scholar
  67. 67.
    Oosterhuis B, ten Berge RJ, Sauerwein HP, et al. Pharmacokinetic-pharmacodynamic modeling of prednisolone-induced lymphocytopenia in man. J Pharmacol Exp Ther 1984; 229(2): 539–46PubMedGoogle Scholar
  68. 68.
    Lew KH, Ludwig EA, Milad MA, et al. Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 1993; 54(4): 402–14PubMedGoogle Scholar
  69. 69.
    Tornatore KM, Logue G, Venuto RC, et al. Pharmacokinetics of methylprednisolone in elderly and young healthy males. J Am Geriate Soc 1994; 42(10): 1118–22Google Scholar
  70. 70.
    Homma M, Oka K, Ikeshima K, et al. Different effects of traditional Chinese medicines containing similar herbal constituents on prednisolone pharmacokinetics. J Pharm Pharmacol 1995; 47(8): 687–92PubMedGoogle Scholar
  71. 71.
    Luippold G, Schneider S, Marto M, et al. Pharmacokinetics of two oral prednisolone tablet formulations in healthy volunteers. Arzneimittel Forschung 2001; 51(11): 911–5PubMedGoogle Scholar
  72. 72.
    Lewis GP, Jusko WJ, Graves L, et al. Prednisone side-effects and serum-protein levels: a collaborative study. Lancet 1971; II(7728): 778–80Google Scholar
  73. 73.
    Benet LZ, Hoener BA. Changes in plasma protein binding have little clinical relevance. Clin Pharmacol Ther 2002; 71(3): 115–21PubMedGoogle Scholar
  74. 74.
    Maser E, Volker B, Friebertshauser J. 11 β-hydroxysteroid dehydrogenase type 1 from human liver: dimerization and enzyme cooperativity support its postulated role as glucocorticoid reductase. Biochemistry 2002; 41(7): 2459–65PubMedGoogle Scholar
  75. 75.
    Diederich S, Hanke B, Burkhardt P, et al. Metabolism of synthetic corticosteroide by 11 β-hydroxysteroid-dehydrogenases in man. Steroids 1998; 63(5–6): 271–7PubMedGoogle Scholar
  76. 76.
    Diederich S, Eigendorff E, Burkhardt P, et al. 11 β-hydroxysteroid dehydrogenase types 1 and 2: an important pharmacokinetic determinant for the activity of synthetic mineralo- and glucocorticoids. J Clin Endocrinol Metab 2002; 87(12): 5695–701PubMedGoogle Scholar
  77. 77.
    Esteban NV, Loughlin T, Yergey AL, et al. Daily Cortisol production rate in man determined by stable isotope dilution/mass spectrometry. J Clin Endocrinol Metab 1991; 72(1): 39–45PubMedGoogle Scholar
  78. 78.
    Lamberts SW, Braining HA, de Jong FH. Corticosteroid therapy in severe illness. N Engl J Med 1997; 337(18): 1285–92PubMedGoogle Scholar
  79. 79.
    N’Gankam V, Uehlinger D, Dick B, et al. Increased Cortisol metabolites and reduced activity of 11 β-hydroxysteroid dehydrogenase in patients on hemodialysis. Kidney Int 2002; 61(5): 1859–66PubMedGoogle Scholar
  80. 80.
    Langhoff E, Olgaard K, Ladefoged J. The immunosuppressive potency in vitro of physiological and synthetic steroids on lymphocyte cultures. Int J Immunopharmacol 1987; 9(4): 469–73PubMedGoogle Scholar
  81. 81.
    Kraan GP, Dullaart RP, Pratt JJ, et al. Kinetics of intravenously dosed Cortisol in four men: consequences for calculation of the plasma Cortisol production rate. J Steroid Biochem Mol Biol 1997; 63(1–3): 139–46PubMedGoogle Scholar
  82. 82.
    Boudinot FD, Jusko WJ. Plasma protein binding interaction of prednisone and prednisolone. J Steroid Biochem 1984; 21(3): 337–9PubMedGoogle Scholar
  83. 83.
    Frey BM, Frey FJ. Clinical pharmacokinetics of prednisone and prednisolone. Clin Pharmacokinet 1990; 19(2): 126–46PubMedGoogle Scholar
  84. 84.
    Magee MH, Blum RA, Lates CD, et al. Prednisolone pharmacokinetics and pharmacodynamics in relation to sex and race. J Clin Pharmacol 2001; 41(11): 1180–94PubMedGoogle Scholar
  85. 85.
    Bartoszek M, Brenner AM, Szefler SJ. Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy. Clin Pharmacol Ther 1987; 42(4): 424–32PubMedGoogle Scholar
  86. 86.
    Wassner SJ, Malekzadeh MH, Pennisi AJ, et al. Allograft survival in patients receiving anticonvulsant medications. Clin Nephrol 1977; 8(1): 293–7PubMedGoogle Scholar
  87. 87.
    Buffington GA, Dominguez JH, Piering WF, et al. Interaction of rifampin and glucocorticoids: adverse effect on renal allograft function. JAMA 1976; 236(17): 1958–60PubMedGoogle Scholar
  88. 88.
    Hollander AA, van Rooij J, Lentjes GW, et al. The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients. Clin Pharmacol Ther 1995; 57(3): 318–24PubMedGoogle Scholar
  89. 89.
    Jeng S, Chanchairujira T, Jusko W, et al. Prednisone metabolism in recipients of kidney or liver transplants and in lung recipients receiving ketoconazole. Transplantation 2003; 75(6): 792–5PubMedGoogle Scholar
  90. 90.
    Ost L. Impairment of prednisolone metabolism by cyclosporine treatment in renal graft recipients. Transplantation 1987; 44(4): 533–5PubMedGoogle Scholar
  91. 91.
    Jusko WJ, Ferron GM, Mis SM, et al. Pharmacokinetics of prednisolone during administration of sirolimus in patients with renal transplants. J Clin Pharmacol 1996; 36(12): 1100–6PubMedGoogle Scholar
  92. 92.
    Ludwig EA, Kong AN, Camara DS, et al. Pharmacokinetics of methylprednisolone hemisuccinate and methylprednisolone in chronic liver disease. J Clin Pharmacol 1993; 33(9): 805–10PubMedGoogle Scholar
  93. 93.
    Periti P, Mazzei T, Mini E, et al. Pharmacokinetic drug interactions of macrolides. Clin Pharmacokinet 1992; 23(2): 106–31PubMedGoogle Scholar
  94. 94.
    LaForce CF, Szefler SJ, Miller MF, et al. Inhibition of methylprednisolone elimination in the presence of erythromycin therapy. J Allergy Clin Immunol 1983; 72(1): 34–9PubMedGoogle Scholar
  95. 95.
    Szefler SJ, Brenner M, Jusko WJ, et al. Dose- and time-related effect of troleandomycin on methylprednisolone elimination. Clin Pharmacol Ther 1982; 32(2): 166–71PubMedGoogle Scholar
  96. 96.
    Kamada AK, Hill MR, Ikle DN, et al. Efficacy and safety of low-dose troleandomycin therapy in children with severe, steroid-requiring asthma. J Allergy Clin Immunol 1993; 91(4): 873–82PubMedGoogle Scholar
  97. 97.
    Zeiger RS, Schatz M, Sperling W, et al. Efficacy of troleandomycin in outpatients with severe, corticosteroid-dependent asthma. J Allergy Clin Immunol 1980; 66(6): 438–46PubMedGoogle Scholar
  98. 98.
    Sirgo MA, Rocci Jr ML, Ferguson RK, et al. Effects of Cimetidine and ranitidine on the conversion of prednisone to prednisolone. Clin Pharmacol Ther 1985; 37(5): 534–8PubMedGoogle Scholar
  99. 99.
    Green AW, Ebling WF, Gardner MJ, et al. Cimetidine-methyl-prednisolone-theophylline metabolic interaction. Am J Med 1984; 77(6): 1115–8PubMedGoogle Scholar
  100. 100.
    Yates CR, Chang C, Kearbey JD, et al. Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res 2003; 20(11): 1794–803PubMedGoogle Scholar
  101. 101.
    Karssen AM, Meijer OC, van der Sandt IC, et al. The role of the efflux transporter P-glycoprotein in brain penetration of prednisolone. J Endocrinol 2002; 175(1): 251–60PubMedGoogle Scholar
  102. 102.
    Koszdin KL, Shen DD, Bernards CM. Spinal cord bioavailability of methylprednisolone after intravenous and intrathecal administration: the role of P-glycoprotein. Anesthesiology 2000; 92(1): 156–63PubMedGoogle Scholar
  103. 103.
    Kovarik JM, Purba HS, Pongowski M, et al. Pharmacokinetics of dexamethasone and valspodar, a P-glycoprotein (MDR1) modulator: implications for coadministration. Pharmacotherapy 1998; 18(6): 1230–6PubMedGoogle Scholar
  104. 104.
    Rose JQ, Yurchak AM, Meikle AW, et al. Effect of smoking on prednisone, prednisolone, and dexamethasone pharmacokinetics. J Pharmacokinet Biopharm 1981; 9(1): 1–14PubMedGoogle Scholar
  105. 105.
    Pascussi JM, Gerbal-Chaloin S, Drocourt L, et al. The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors. Biochim Biophys Acta 2003; 1619(3): 243–53PubMedGoogle Scholar
  106. 106.
    McCune JS, Hawke RL, LeCluyse EL, et al. In vivo and in vitro induction of human cytochrome P4503a4 by dexamethasone. Clin Pharmacol Ther 2000; 68(4): 356–66PubMedGoogle Scholar
  107. 107.
    Villikka K, Rivisto KT, Neuvonen PJ. The effect of dexamethasone on the pharmacokinetics of triazolam. Pharmacol Toxicol 1998; 83(3): 135–8PubMedGoogle Scholar
  108. 108.
    Villikka K, Varis T, Backman JT, et al. Effect of methylprednisolone on CYP3A4-mediated drug metabolism in vivo. Eur J Clin Pharmacol 2001; 57(6–7): 457–60PubMedGoogle Scholar
  109. 109.
    Yates CR, Vysokanov A, Mukherjee A, et al. Time-variant increase in methylprednisolone clearance in patients with acute respiratory distress syndrome: a population pharmacokinetic study. J Clin Pharmacol 2001; 41(4): 415–24PubMedGoogle Scholar
  110. 110.
    Shimada T, Terada A, Yokogawa K, et al. Lowered blood concentration of tacrolimus and its recovery with changes in expression of CYP3A and P-glycoprotein after high-dose steroid therapy. Transplantation 2002; 74(10): 1419–24PubMedGoogle Scholar
  111. 111.
    Lackner TE. Interaction of dexamethasone with phenytoin. Pharmacotherapy 1991; 11(4): 344–7PubMedGoogle Scholar
  112. 112.
    Cattaneo D, Perico N, Gaspari F, et al. Glucocorticoids interfere with mycophenolate mofetil bioavailability in kidney transplantation. Kidney Int 2002; 62(3): 1060–7PubMedGoogle Scholar
  113. 113.
    Schuetz EG, Hazelton GA, Hall J, et al. Induction of digitoxigenin monodigitoxoside UDP-glucuronosyltransferase activity by glucocorticoids and other inducers of cytochrome P-450p in primary monolayer cultures of adult rat hepatocytes and in human liver. J Biol Chem 1986; 261(18): 8270–5PubMedGoogle Scholar
  114. 114.
    Frey FJ, Schnetzer A, Horber FF, et al. Evidence that cyclosporine does not affect the metabolism of prednisolone after renal transplantation. Transplantation 1987; 43(4): 494–8PubMedGoogle Scholar
  115. 115.
    Rocci Jr ML, Tietze KJ, Lee J, et al. The effect of cyclosporine on the pharmacokinetics of prednisolone in renal transplant patients. Transplantation 1988; 45(3): 656–60PubMedGoogle Scholar
  116. 116.
    Ptachcinski RJ, Venkataramanan R, Burckart GJ, et al. Cyclosporine: high-dose steroid interaction in renal transplant recipients: assessment by HPLC. Transplant Proc 1987; 19 (1 Pt 2): 1728–9PubMedGoogle Scholar
  117. 117.
    Klintmalm G, Sawe J, Ringden O, et al. Cyclosporine plasma levels in renal transplant patients: association with renal toxicity and allograft rejection. Transplantation 1985; 39(2): 132–7PubMedGoogle Scholar
  118. 118.
    Arnold JC, O’Grady JG, Tredger JM, et al. Effects of low-dose prednisolone on cyclosporine pharmacokinetics in liver transplant recipients: radioimmunoassay with specific and nonspecific monoclonal antibodies. Eur J Clin Pharmacol 1990; 39(3): 257–60PubMedGoogle Scholar
  119. 119.
    Backman L, Kreis H, Morales JM, et al. Sirolimus steady-state trough concentrations are not affected by bolus methylprednisolone therapy in renal allograft recipients. Br J Clin Pharmacol 2002; 54(1): 65–8PubMedGoogle Scholar
  120. 120.
    Chamberlain CE, Kirk AD, Hale D, et al. Prednisone decreases sensitivity to sirolimus in kidney transplant recipients [abstract]. Am J Transplant 2003; 3 Suppl. 5: 354Google Scholar
  121. 121.
    Frey FJ, Gambertoglio JG, Frey BM, et al. Nonlinear plasma protein binding and haemodialysis clearance of prednisolone. Eur J Clin Pharmacol 1982; 23(1): 65–74PubMedGoogle Scholar
  122. 122.
    Sherlock JE, Letteri JM. Effect of hemodialysis on methylprednisolone plasma levels. Nephron 1977; 18(4): 208–11PubMedGoogle Scholar
  123. 123.
    Bergrem H. Pharmacokinetics and protein binding of prednisolone in patients with nephrotic syndrome and patients undergoing hemodialysis. Kidney Int 1983; 23(6): 876–81PubMedGoogle Scholar
  124. 124.
    Schwab M, Klotz U. Pharmacokinetic considerations in the treatment of inflammatory bowel disease. Clin Pharmacokinet 2001; 40(10): 723–51PubMedGoogle Scholar
  125. 125.
    Milsap RL, George DE, Szefler SJ, et al. Effect of inflammatory bowel disease on absorption and disposition of prednisolone. Dig Dis Sci 1983; 28(2): 161–8PubMedGoogle Scholar
  126. 126.
    Dove AM, Szefler SJ, Hill MR, et al. Altered prednisolone pharmacokinetics in patients with cystic fibrosis. J Pediatr 1992; 120(5): 789–94PubMedGoogle Scholar
  127. 127.
    Rose JQ, Nickelsen JA, Middleton Jr E, et al. Prednisolone disposition in steroid-dependent asthmatics. J Allergy Clin Immunol 1980; 66(5): 366–73PubMedGoogle Scholar
  128. 128.
    Petersen KB, Jusko WJ, Rasmussen M, et al. Population pharmacokinetics of prednisolone in children with acute lymphoblastic leukemia. Cancer Chemother Pharmacol 2003; 51(6): 465–73PubMedGoogle Scholar
  129. 129.
    Segal JL, Maltby BF, Langdorf MI, et al. Methylprednisolone disposition kinetics in patients with acute spinal cord injury. Pharmacotherapy 1998; 18(1): 16–22PubMedGoogle Scholar
  130. 130.
    Newton R. Molecular mechanisms of glucocorticoid action: what is important? Thorax 2000; 55(7): 603–13PubMedGoogle Scholar
  131. 131.
    Buttgereit F, Wehling M, Burmester GR. A new hypothesis of modular glucocorticoid actions: steroid treatment of rheumatic diseases revisited. Arthritis Rheum 1998; 41(5): 761–7PubMedGoogle Scholar
  132. 132.
    Colbert RA, Young DA. Glucocorticoid-induced messenger ribonucleic acids in rat thymic lymphocytes: rapid primary effects specific for glucocorticoids. Endocrinology 1986; 119(6): 2598–605PubMedGoogle Scholar
  133. 133.
    Jin JY, Almon RR, DuBois DC, et al. Modeling of corticosteroid pharmacogenomics in rat liver using gene microarrays. J Pharmacol Exp Ther 2003; 307(1): 93–109PubMedGoogle Scholar
  134. 134.
    Almon RR, DuBois DC, Brandenburg EH, et al. Pharmacodynamics and pharmacogenomics of diverse receptor-mediated effects of methylprednisolone in rats using microarray analysis. J Pharmacokinet Pharmacodyn 2002; 29(2): 103–29PubMedGoogle Scholar
  135. 135.
    Galon J, Franchimont D, Hiroi N, et al. Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells. FASEB J 2002; 16(1): 61–71PubMedGoogle Scholar
  136. 136.
    Croxtall JD, Choudhury Q, Flower RJ. Glucocorticoids act within minutes to inhibit recruitment of signalling factors to activated EGF receptors through a receptor-dependent, transcription-independent mechanism. Br J Pharmacol 2000; 130(2): 289–98PubMedGoogle Scholar
  137. 137.
    Tanioka T, Nakatani Y, Semmyo N, et al. Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. J Biol Chem 2000; 275(42): 32775–82PubMedGoogle Scholar
  138. 138.
    Ylikomi T, Wurtz JM, Syvala H, et al. Reappraisal of the role of heat shock proteins as regulators of steroid receptor activity. Crit Rev Biochem Mol Biol 1998; 33(6): 437–66PubMedGoogle Scholar
  139. 139.
    Lieberman BA, Nordeen SK. DNA intersegment transfer, how steroid receptors search for a target site. J Biol Chem 1997; 272(2): 1061–8PubMedGoogle Scholar
  140. 140.
    Evans RM. The steroid and thyroid hormone receptor superfamily. Science 1988; 240(4854): 889–95PubMedGoogle Scholar
  141. 141.
    Rogatsky I, Luecke HF, Leitman DC, et al. Alternate surfaces of transcriptional coregulator GRIP1 function in different glucocorticoid receptor activation and repression contexts. Proc Natl Acad Sci USA 2002; 99(26): 16701–6PubMedGoogle Scholar
  142. 142.
    Rosenfeld MG, Glass CK. Coregulator codes of transcriptional regulation by nuclear receptors. J Biol Chem 2001; 276(40): 36865–8PubMedGoogle Scholar
  143. 143.
    Bodwell JE, Webster JC, Jewell CM, et al. Glucocorticoid receptor phosphorylation: overview, function and cell cycledependence. J Steroid Biochem Mol Biol 1998; 65(1–6): 91–9PubMedGoogle Scholar
  144. 144.
    Irusen E, Matthews JG, Takahashi A, et al. P38 mitogenactivated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol 2002; 109(4): 649–57PubMedGoogle Scholar
  145. 145.
    DeFranco DB. Navigating steroid hormone receptors through the nuclear compartment. Mol Endocrinol 2002; 16(7): 1449–55PubMedGoogle Scholar
  146. 146.
    Pandit S, Geissler W, Harris G, et al. Allosteric effects of dexamethasone and RU486 on glucocorticoid receptor-DNA interactions. J Biol Chem 2002; 277(2): 1538–43PubMedGoogle Scholar
  147. 147.
    Denk A, Goebeler M, Schmid S, et al. Activation of NF-κB via the IκB kinase complex is both essential and sufficient for proinflammatory gene expression in primary endothelial cells. J Biol Chem 2001; 276(30): 28451–8PubMedGoogle Scholar
  148. 148.
    Vermeulen L, De Wilde G, Notebaert S, et al. Regulation of the transcriptional activity of the nuclear factor-κB p65 subunit. Biochem Pharmacol 2002; 64(5–6): 963–70PubMedGoogle Scholar
  149. 149.
    Lawrence T, Willoughby DA, Gilroy DW. Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat Rev Immunol 2002; 2(10): 787–95PubMedGoogle Scholar
  150. 150.
    Kagoshima M, Ito K, Cosio B, et al. Glucocorticoid suppression of nuclear factor-κB: a role for histone modifications. Biochem Soc Trans 2003; 31 Pt 1: 60–5PubMedGoogle Scholar
  151. 151.
    Ito K, Barnes PJ, Adcock IM. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1 β-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol 2000; 20(18): 6891–903PubMedGoogle Scholar
  152. 152.
    Scheinman RI, Cogswell PC, Lofquist AK, et al. Role of transcriptional activation of IκBα in mediation of immunosuppression by glucocorticoids. Science 1995; 270(5234): 283–6PubMedGoogle Scholar
  153. 153.
    Poon M, Liu B, Taubman MB. Identification of a novel dexamethasone-sensitive RNA-destabilizing region on rat monocyte chemoattractant protein 1 mRNA. Mol Cell Biol 1999; 19(10): 6471–8PubMedGoogle Scholar
  154. 154.
    Newton R, Seybold J, Kuitert LM, et al. Repression of cyclooxygenase-2 and prostaglandin E2 release by dexamethasone occurs by transcriptional and post-transcriptional mechanisms involving loss of polyadenylated mRNA. J Biol Chem 1998; 273(48): 32312–21PubMedGoogle Scholar
  155. 155.
    Hammes SR. The further redefining of steroid-mediated signaling. Proc Natl Acad Sci USA 2003; 100(5): 2168–70PubMedGoogle Scholar
  156. 156.
    Zhu Y, Rice CD, Pang Y, et al. Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. Proc Natl Acad Sci USA 2003; 100(5): 2231–6PubMedGoogle Scholar
  157. 157.
    Buttgereit F, Scheffold A. Rapid glucocorticoid effects on immune cells. Steroids 2002; 67(6): 529–34PubMedGoogle Scholar
  158. 158.
    Hinz B, Hirschelmann R. Rapid non-genomic feedback effects of glucocorticoids on CRF-induced ACTH secretion in rats. Pharm Res 2000; 17(10): 1273–7PubMedGoogle Scholar
  159. 159.
    Falkenstein E, Tillmann HC, Christ M, et al. Multiple actions of steroid hormones: a focus on rapid, nongenomic effects. Pharmacol Rev 2000; 52(4): 513–56PubMedGoogle Scholar
  160. 160.
    Croxtall JD, van Hal PT, Choudhury Q, et al. Different glucocorticoids vary in their genomic and non-genomic mechanism of action in A549 cells. Br J Pharmacol 2002; 135(2): 511–9PubMedGoogle Scholar
  161. 161.
    Buttgereit F, Brand MD, Burmester GR. Equivalent doses and relative drug potencies for non-genomic glucocorticoid effects: a novel glucocorticoid hierarchy. Biochem Pharmacol 1999; 58(2): 363–8PubMedGoogle Scholar
  162. 162.
    Croxtall JD, Gilroy DW, Solito E, et al. Attenuation of glucocorticoid functions in an ANX-A1 −/− cell line. Biochem J 2003; 371 Pt 3: 927–35PubMedGoogle Scholar
  163. 163.
    Whiting KP, Restall CJ, Brain PF. Steroid hormone-induced effects on membrane fluidity and their potential roles in nongenomic mechanisms. Life Sci 2000; 67(7): 743–57PubMedGoogle Scholar
  164. 164.
    Lamche HR, Silberstein PT, Knabe AC, et al. Steroids decrease granulocyte membrane fluidity, while phorbol ester increases membrane fluidity: studies using electron paramagnetic resonance. Inflammation 1990; 14(1): 61–70PubMedGoogle Scholar
  165. 165.
    Hinz B, Hirschelmann R. Dexamethasone megadoses stabilize rat liver lysosomal membranes by non-genomic and genomic effects. Pharm Res 2000; 17(12): 1489–93PubMedGoogle Scholar
  166. 166.
    Almawi WY, Beyhum HN, Rahme AA, et al. Regulation of cytokine and cytokine receptor expression by glucocorticoids. J Leukoc Biol 1996; 60(5): 563–72PubMedGoogle Scholar
  167. 167.
    Khan WA, Blobe GC, Hannun YA. Arachidonic acid and free fatty acids as second messengers and the role of protein kinase C. Cell Signal 1995; 7(3): 171–84PubMedGoogle Scholar
  168. 168.
    Newton R, Kuitert LM, Slater DM, et al. Cytokine induction of cytosolic phospholipase a2 and cyclooxygenase-2 mRNA is suppressed by glucocorticoids in human epithelial cells. Life Sci 1997; 60(1): 67–78PubMedGoogle Scholar
  169. 169.
    Matsumura M, Kakishita H, Suzuki M, et al. Dexamethasone suppresses iNOS gene expression by inhibiting NF-κB in vascular smooth muscle cells. Life Sci 2001; 69(9): 1067–77PubMedGoogle Scholar
  170. 170.
    Shinoda J, McLaughlin KE, Bell HS, et al. Molecular mechanisms underlying dexamethasone inhibition of iNOS expression and activity in C6 glioma cells. Glia 2003; 42(1): 68–76PubMedGoogle Scholar
  171. 171.
    Linnane SJ, Thin AG, Keatings VM, et al. Glucocorticoid treatment reduces exhaled nitric oxide in cystic fibrosis patients. Eur Respir J 2001; 17(6): 1267–70PubMedGoogle Scholar
  172. 172.
    Moodley YP, Chetty R, Lalloo UG. Nitric oxide levels in exhaled air and inducible nitric oxide synthase immunolocalization in pulmonary sarcoidosis. Eur Respir J 1999; 14(4): 822–7PubMedGoogle Scholar
  173. 173.
    Pitzalis C, Pipitene N, Perretti M. Regulation of leukocyteendothelial interactions by glucocorticoids. Ann N Y Acad Sci 2002; 966: 108–18PubMedGoogle Scholar
  174. 174.
    Atsuta J, Plitt J, Bochner BS, et al. Inhibition of VCAM-1 expression in human bronchial epithelial cells by glucocorticoids. Am J Respir Cell Mol Biol 1999; 20(4): 643–50PubMedGoogle Scholar
  175. 175.
    Cronstein BN, Kimmel SC, Levin RI, et al. A mechanism for the antiinflammatory effects of corticosteroids: the glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1. Proc Natl Acad Sci USA 1992; 89(21): 9991–5PubMedGoogle Scholar
  176. 176.
    Goulding NJ, Ogbourn S, Pipitene N, et al. The inhibitory effect of dexamethasone on lymphocyte adhesion molecule expression and intercellular aggregation is not mediated by lipocortin 1. Clin Exp Immunol 1999; 118(3): 376–83PubMedGoogle Scholar
  177. 177.
    Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells. Nat Rev Immunol 2003; 3(3): 253–7PubMedGoogle Scholar
  178. 178.
    Levings MK, Sangregorio R, Sartirana C, et al. Human CD25+CD4+ T suppressor cell clones produce transforming growth factor β, but not interleukin 10, and are distinct from type 1 T regulatory cells. J Exp Med 2002; 196(10): 1335–46PubMedGoogle Scholar
  179. 179.
    Filaci G, Suciu-Foca N. CD8+ T suppressor cells are back to the game: are they players in autoimmunity? Autoimmun Rev 2002; 1(5): 279–83PubMedGoogle Scholar
  180. 180.
    Santana MA, Rosenstein Y. What it takes to become an effector T cell: the process, the cells involved, and the mechanisms. J Cell Physiol 2003; 195(3): 392–401PubMedGoogle Scholar
  181. 181.
    Lechler RI, Garden OA, Turka LA. The complementary roles of deletion and regulation in transplantation tolerance. Nat Rev Immunol 2003; 3(2): 147–58PubMedGoogle Scholar
  182. 182.
    Chen W, Wahl SM. TGF-β: the missing link in CD4(+)CD25(+) regulatory T cell-mediated immunosuppression. Cytokine Growth Factor Rev 2003; 14(2): 85–9PubMedGoogle Scholar
  183. 183.
    Kalthoff FS, Chung J, Musser P, et al. Pimecrolimus does not affect the differentiation, maturation and function of human monocyte-derived dendritic cells, in contrast to corticosteroids. Clin Exp Immunol 2003; 133(3): 350–9PubMedGoogle Scholar
  184. 184.
    Rea D, van Kooten C, van Meijgaarden KE, et al. Glucocorticoids transform CD40-triggering of dendritic cells into an alternative activation pathway resulting in antigen-presenting cells that secrete IL-10. Blood 2000; 95(10): 3162–7PubMedGoogle Scholar
  185. 185.
    Dong X, Bachman LA, Kumar R, et al. Generation of antigenspecific, interleukin-10-producing T-cells using dendritic cell stimulation and steroid hormone conditioning. Transpl Immunol 2003; 11(3–4): 323–33PubMedGoogle Scholar
  186. 186.
    Barrat FJ, Cua DJ, Boonstra A, et al. In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med 2002; 195(5): 603–16PubMedGoogle Scholar
  187. 187.
    Terada Y, Okado T, Inoshita S, et al. Glucocorticoids stimulate p21(CIP1) in mesangial cells and in anti-GBM glomerulonephritis. Kidney Int 2001; 59(5): 1706–16PubMedGoogle Scholar
  188. 188.
    Goke MN, Schneider M, Beil W, et al. Differential glucocorticoid effects on repair mechanisms and NF-κB activity in the intestinal epithelium. Regul Pept 2002; 105(3): 203–14PubMedGoogle Scholar
  189. 189.
    Amsterdam A, Tajima K, Sasson R. Cell-specific regulation of apoptosis by glucocorticoids: implication to their anti-inflammatory action. Biochem Pharmacol 2002; 64(5–6): 843–50PubMedGoogle Scholar
  190. 190.
    Leussink VI, Jung S, Merschdorf U, et al. High-dose methylprednisolone therapy in multiple sclerosis induces apoptosis in peripheral blood leukocytes. Arch Neurol 2001; 58(1): 91–7PubMedGoogle Scholar
  191. 191.
    Migita K, Eguchi K, Kawabe Y, et al. Apoptosis induction in human peripheral blood T lymphocytes by high-dose steroid therapy. Transplantation 1997; 63(4): 583–7PubMedGoogle Scholar
  192. 192.
    Schmidt J, Gold R, Schonrock L, et al. T-cell apoptosis in situ in experimental autoimmune encephalomyelitis following methylprednisolone pulse therapy. Brain 2000; 123 Pt 7: 1431–41PubMedGoogle Scholar
  193. 193.
    Zhang X, Moilanen E, Adcock IM, et al. Divergent effect of mometasone on human eosinophil and neutrophil apoptosis. Life Sci 2002; 71(13): 1523–34PubMedGoogle Scholar
  194. 194.
    Meagher LC, Cousin JM, Seckl JR, et al. Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. J Immunol 1996; 156(11): 4422–8PubMedGoogle Scholar
  195. 195.
    Baichwal VR, Baeuerle PA. Activate NF-κB or die? Curr Biol 1997; 7(2): R94–6PubMedGoogle Scholar
  196. 196.
    Stankova J, Turcotte S, Harris J, et al. Modulation of leukotriene B4 receptor-1 expression by dexamethasone: potential mechanism for enhanced neutrophil survival. J Immunol 2002; 168(7): 3570–6PubMedGoogle Scholar
  197. 197.
    Webster JC, Huber RM, Hanson RL, et al. Dexamethasone and tumor necrosis factor-α act together to induce the cellular inhibitor of apoptosis-2 gene and prevent apoptosis in a variety of cell types. Endocrinology 2002; 143(10): 3866–74PubMedGoogle Scholar
  198. 198.
    Kuroda M, Sasamura H, Shimizu-Hirota R, et al. Glucocorticoid regulation of proteoglycan synthesis in mesangial cells. Kidney Int 2002; 62(3): 780–9PubMedGoogle Scholar
  199. 199.
    Kasinath BS, Singh AK, Kanwar YS, et al. Dexamethasone increases heparan sulfate proteoglycan core protein content of glomerular epithelial cells. J Lab Clin Med 1990; 115(2): 196–202PubMedGoogle Scholar
  200. 200.
    Russell RE, Culpitt SV, DeMatos C, et al. Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2002; 26(5): 602–9PubMedGoogle Scholar
  201. 201.
    Perretti M, Ahluwalia A. The microcirculation and inflammation: site of action for glucocorticoids. Microcirculation 2000; 7(3): 147–61PubMedGoogle Scholar
  202. 202.
    Perretti M, Chiang N, La M, et al. Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Nat Med 2002; 8(11): 1296–302PubMedGoogle Scholar
  203. 203.
    Stelmach I, Jerzynska J, Kuna P. A randomized, double-blind trial of the effect of glucocorticoid, antileukotriene and β-agonist treatment on IL-10 serum levels in children with asthma. Clin Exp Allergy 2002; 32(2): 264–9PubMedGoogle Scholar
  204. 204.
    Asadullah K, Sterry W, Volk HD. Interleukin-10 therapy: review of a new approach. Pharmacol Rev 2003; 55(2): 241–69PubMedGoogle Scholar
  205. 205.
    Segerer S, Cui Y, Eitner F, et al. Expression of chemokines and chemokine receptors during human renal transplant rejection. Am J Kidney Dis 2001; 37(3): 518–31PubMedGoogle Scholar
  206. 206.
    Game DS, Lechler RI. Pathways of allorecognition: implications for transplantation tolerance. Transpl Immunol 2002; 10(2–3): 101–8PubMedGoogle Scholar
  207. 207.
    Pan J, Ju D, Wang Q, et al. Dexamethasone inhibits the antigen presentation of dendritic cells in MHC class II pathway. Immunol Lett 2001; 76(3): 153–61PubMedGoogle Scholar
  208. 208.
    Almawi WY, Lipman ML, Stevens AC, et al. Abrogation of glucocorticoid-mediated inhibition of t cell proliferation by the synergistic action of IL-1, IL-6, and IFN-γ. J Immunol 1991; 146(10): 3523–7PubMedGoogle Scholar
  209. 209.
    Park SY, Kim HW, Moon KC, et al. mRNA expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in acute renal allograft rejection. Transplantation 2000; 69(12): 2554–60PubMedGoogle Scholar
  210. 210.
    Frauman AG. An overview of the adverse reactions to adrenal corticosteroids. Adverse Drug React Toxicol Rev 1996; 15(4): 203–6PubMedGoogle Scholar
  211. 211.
    Schacke H, Docke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 2002; 96(1): 23–43PubMedGoogle Scholar
  212. 212.
    Whitworth JA, Gordon D, Andrews J, et al. The hypertensive effect of synthetic glucocorticoids in man: role of sodium and volume. J Hypertens 1989; 7(7): 537–49PubMedGoogle Scholar
  213. 213.
    Brem AS. Insights into glucocorticoid-associated hypertension. Am J Kidney Dis 2001; 37(1): 1–10PubMedGoogle Scholar
  214. 214.
    Bicknell AB. Identification of the adrenal protease that cleaves pro-γ-MSH: the dawning of a new era in adrenal physiology? J Endocrinol 2002; 172(3): 405–10PubMedGoogle Scholar
  215. 215.
    Schlaghecke R, Kornely E, Santen RT, et al. The effect of longterm glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone. N Engl J Med 1992; 326(4): 226–30PubMedGoogle Scholar
  216. 216.
    Agusti C, Rano A, Fileila X, et al. Pulmonary infiltrates in patients receiving long-term glucocorticoid treatment: etiology, prognostic factors, and associated inflammatory response. Chest 2003; 123(2): 488–98PubMedGoogle Scholar
  217. 217.
    Porges AJ, Beattie SL, Ritchlin C, et al. Patients with systemic lupus erythematosus at risk for Pneumocystis carinii pneumonia. J Rheumatol 1992; 19(8): 1191–4PubMedGoogle Scholar
  218. 218.
    Canalis E, Delany AM. Mechanisms of glucocorticoid action in bone. Ann N Y Acad Sci 2002; 966: 73–81PubMedGoogle Scholar
  219. 219.
    Engelbrecht Y, de Wet H, Horsch K, et al. Glucocorticoids induce rapid up-regulation of mitogen-activated protein kinase phosphatase-1 and dephosphorylation of extracellular signalregulated kinase and impair proliferation in human and mouse osteoblast cell lines. Endocrinology 2003; 144(2): 412–22PubMedGoogle Scholar
  220. 220.
    Van Staa TP, Leufkens HG, Abenhaim L, et al. Use of oral corticosteroids and risk of fractures. J Bone Miner Res 2000; 15(6): 993–1000PubMedGoogle Scholar
  221. 221.
    van Staa TP, Leufkens HG, Abenhaim L, et al. Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxf) 2000; 39(12): 1383–9Google Scholar
  222. 222.
    Garcia Rodriguez LA, Hernandez-Diaz S. The risk of upper gastrointestinal complications associated with nonsteroidal anti-inflammatory drugs, glucocorticoids, acetaminophen, and combinations of these agents. Arthritis Res 2001; 3(2): 98–101PubMedGoogle Scholar
  223. 223.
    Guslandi M, Tittobello A. Steroid ulcers: a myth revisited. BMJ 1992; 304(6828): 655–6PubMedGoogle Scholar
  224. 224.
    Jobling AI, Augusteyn RC. What causes steroid cataracts? A review of steroid-induced posterior subcapsular cataracts. Clin Exp Optom 2002; 85(2): 61–75PubMedGoogle Scholar
  225. 225.
    Vreden SG, Hermus AR, van Liessum PA, et al. Aseptic bone necrosis in patients on glucocorticoid replacement therapy. Neth J Med 1991; 39(3–4): 153–7PubMedGoogle Scholar
  226. 226.
    Ahmed SF, Tucker P, Mushtaq T, et al. Short-term effects on linear growth and bone turnover in children randomized to receive prednisolone or dexamethasone. Clin Endocrinol (Oxf) 2002; 57(2): 185–91Google Scholar
  227. 227.
    Ventura MT, Calogiuri GF, Matino MG, et al. Alternative glucocorticoids for use in cases of adverse reaction to systemic glucocorticoids: a study on 10 patients. Br J Dermatol 2003; 148(1): 139–41PubMedGoogle Scholar
  228. 228.
    Twycross R. The risks and benefits of corticosteroids in advanced cancer. Drug Saf 1994; 11(3): 163–78PubMedGoogle Scholar
  229. 229.
    Wilson AM, Lipworth BJ. Short-term dose-response relationships for the relative systemic effects of oral prednisolone and inhaled fluticasone in asthmatic adults. Br J Clin Pharmacol 1999; 48(4): 579–85PubMedGoogle Scholar
  230. 230.
    Vermeer H, Hendriks-Stegeman BI, van der Burg B, et al. Glucocorticoid-induced increase in lymphocytic FKBP51 messenger ribonucleic acid expression: a potential marker for glucocorticoid sensitivity, potency, and bioavailability. J Clin Endocrinol Metab 2003; 88(1): 277–84PubMedGoogle Scholar
  231. 231.
    Jaffuel D, Roumestan C, Balaguer P, et al. Correlation between different gene expression assays designed to measure transactivation potencies of systemic glucocorticoids. Steroids 2001; 66(7): 597–604PubMedGoogle Scholar
  232. 232.
    Santini G, Patrignani P, Sciulli MG, et al. The human pharmacology of monocyte cyclooxygenase 2 inhibition by Cortisol and synthetic glucocorticoids. Clin Pharmacol Ther 2001; 70(5): 475–83PubMedGoogle Scholar
  233. 233.
    Jaffuel D, Demoly P, Gougat C, et al. Transcriptional potencies of inhaled glucocorticoids. Am J Respir Crit Care Med 2000; 162(1): 57–63PubMedGoogle Scholar
  234. 234.
    Hogger P, Erpenstein U, Rohdewald P, et al. Biochemical characterization of a glucocorticoid-induced membrane protein (RM3/1) in human monocytes and its application as model system for ranking glucocorticoid potency. Pharm Res 1998; 15(2): 296–302PubMedGoogle Scholar
  235. 235.
    Oehling AG, Akdis CA, Schapowal A, et al. Suppression of the immune system by oral glucocorticoid therapy in bronchial asthma. Allergy 1997; 52(2): 144–54PubMedGoogle Scholar
  236. 236.
    Ducloux D, Carron PL, Motte G, et al. Lymphocyte subsets and assessment of cancer risk in renal transplant recipients. Transpl Int 2002; 15(8): 393–6PubMedGoogle Scholar
  237. 237.
    Ducloux D, Carron PL, Rebibou JM, et al. CD4 lymphocytopenia as a risk factor for skin cancers in renal transplant recipients. Transplantation 1998; 65(9): 1270–2PubMedGoogle Scholar
  238. 238.
    Ducloux D, Challier B, Saas P, et al. CD4 cell lymphopenia and atherosclerosis in renal transplant recipients. J Am Soc Nephrol 2003; 14(3): 767–72PubMedGoogle Scholar
  239. 239.
    Chakraborty A, Jusko WJ. Pharmacodynamic interaction of recombinant human interleukin-10 and prednisolone using in vitro whole blood lymphocyte proliferation. J Pharm Sci 2002; 91(5): 1334–42PubMedGoogle Scholar
  240. 240.
    Ramakrishnan R, Jusko WJ. Interactions of aspirin and salicylic acid with prednisolone for inhibition of lymphocyte proliferation. Int Immunopharmacol 2001; 1(11): 2035–42PubMedGoogle Scholar
  241. 241.
    Singh GJ, Adams WP, Lesko LJ, et al. Development of in vivobioequivalence methodology for dermatologic corticosteroids based on pharmacodynamic modeling. Clin Pharmacol Ther 1999; 66(4): 346–57PubMedGoogle Scholar
  242. 242.
    Kelly HW. Establishing a therapeutic index for the inhaled corticosteroids (Pt I): pharmacokinetic/pharmacodynamic comparison of the inhaled corticosteroids. J Allergy Clin Immunol 1998; 102 (4 Pt 2): S36–51PubMedGoogle Scholar
  243. 243.
    Meikle AW, Tyler FH. Potency and duration of action of glucocorticoids: effects of hydrocortisone, prednisone and dexamethasone on human pituitary-adrenal function. Am J Med 1977; 63(2): 200–7PubMedGoogle Scholar
  244. 244.
    Yudt MR, Cidlowski JA. The glucocorticoid receptor: coding a diversity of proteins and responses through a single gene. Mol Endocrinol 2002; 16(8): 1719–26PubMedGoogle Scholar
  245. 245.
    Ito K, Caramori G, Lim S, et al. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med 2002; 166(3): 392–6PubMedGoogle Scholar
  246. 246.
    Hochhaus G, Mollmann H, Derendorf H, et al. Pharmacokinetic/pharmacodynamic aspects of aerosol therapy using glucocorticoids as a model. J Clin Pharmacol 1997; 37(10): 881–92PubMedGoogle Scholar
  247. 247.
    Mager DE, Moledina N, Jusko WJ. Relative immunosuppressive potency of therapeutic corticosteroids measured by whole blood lymphocyte proliferation. J Pharm Sci 2003; 92(7): 1521–5PubMedGoogle Scholar
  248. 248.
    Kuhnke A, Burmester GR, Krauss S, et al. Bioenergetics of immune cells to assess rheumatic disease activity and efficacy of glucocorticoid treatment. Ann Rheum Dis 2003; 62(2): 133–9PubMedGoogle Scholar
  249. 249.
    Czock D, Giehl M, Keller F. A concept for pharmacokineticpharmacodynamic dosage adjustment in renal impairment: the case of aminoglycosides. Clin Pharmacokinet 2000; 38(4): 367–75PubMedGoogle Scholar
  250. 250.
    Ferron GM, Jusko WJ. Species- and gender-related differences in cyclosporine/prednisolone/sirolimus interactions in whole blood lymphocyte proliferation assays. J Pharmacol Exp Ther 1998; 286(1): 191–200PubMedGoogle Scholar
  251. 251.
    Markham A, Faulds D. Theophylline: a review of its potential steroid sparing effects in asthma. Drugs 1998; 56(6): 1081–91PubMedGoogle Scholar
  252. 252.
    Ito K, Lim S, Caramori G, et al. A molecular mechanism of action of theophylline: induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci USA 2002; 99(13): 8921–6PubMedGoogle Scholar
  253. 253.
    Ito K, Lim S, Caramori G, et al. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J 2001; 15(6): 1110–2PubMedGoogle Scholar
  254. 254.
    Spahn JD, Fost DA, Covar R, et al. Clarithromycin potentiates glucocorticoid responsiveness in patients with asthma: results of a pilot study. Ann Allergy Asthma Immunol 2001; 87(6): 501–5PubMedGoogle Scholar
  255. 255.
    Roth M, Johnson PR, Rudiger JJ, et al. Interaction between glucocorticoids and β2 agonists on bronchial airway smooth muscle cells through synchronised cellular signalling. Lancet 2002; 360(9342): 1293–9PubMedGoogle Scholar
  256. 256.
    Boxenbaum H. Pharmacokinetics: philosophy of modeling. Drug Metab Rev 1992; 24(1): 89–120PubMedGoogle Scholar
  257. 257.
    DeStefano III JJ, Landaw EM. Multiexponential, multicompartmental, and noncompartmental modeling. I: methodological limitations and physiological interpretations. Am J Physiol 1984; 246 (5 Pt 2): R651–64Google Scholar
  258. 258.
    Meibohm B, Hochhaus G, Mollmann H, et al. A pharmacokinetic/pharmacodynamic approach to predict the cumulative Cortisol suppression of inhaled corticosteroids. J Pharmacokinet Biopharm 1999; 27(2): 127–47PubMedGoogle Scholar
  259. 259.
    Nichols AI, Jusko WJ. Receptor-mediated prednisolone pharmacodynamics in rats: model verification using a dosesparing regimen. J Pharmacokinet Biopharm 1990; 18(3): 189–208PubMedGoogle Scholar
  260. 260.
    Chan PL, Holford NH. Drug treatment effects on disease progression. Annu Rev Pharmacol Toxicol 2001; 41: 625–59PubMedGoogle Scholar
  261. 261.
    Dayneka NL, Garg V, Jusko WJ. Comparison of four basic models of indirect pharmacodynamic responses. J Pharmacokinet Biopharm 1993; 21(4): 457–78PubMedGoogle Scholar
  262. 262.
    Jusko WJ, Ko HC, Ebling WF. Convergence of direct and indirect pharmacodynamic response models. J Pharmacokinet Biopharm 1995; 23(1): 5–8PubMedGoogle Scholar
  263. 263.
    Levy G. Mechanism-based pharmacodynamic modeling. Clin Pharmacol Ther 1994; 56(4): 356–8PubMedGoogle Scholar
  264. 264.
    Sun YN, Jusko WJ. Transit compartments versus gamma distribution function to model signal transduction processes in pharmacodynamics. J Pharm Sci 1998; 87(6): 732–7PubMedGoogle Scholar
  265. 265.
    Nielsen HK, Charles P, Mosekilde L. The effect of single oral doses of prednisone on the circadian rhythm of serum osteocalcin in normal subjects. J Clin Endocrinol Metab 1988; 67(5): 1025–30PubMedGoogle Scholar
  266. 266.
    Chakraborty A, Krzyzanski W, Jusko WJ. Mathematical modeling of circadian Cortisol concentrations using indirect response models: comparison of several methods. J Pharmacokinet Biopharm 1999; 27(1): 23–43PubMedGoogle Scholar
  267. 267.
    Rohatagi S, Tauber U, Richter K, et al. Pharmacokinetic/pharmacodynamic modeling of Cortisol suppression after oral administration of fluocortolone. J Clin Pharmacol 1996; 36(4): 311–4PubMedGoogle Scholar
  268. 268.
    Rohatagi S, Bye A, Mackie AE, et al. Mathematical modeling of Cortisol circadian rhythm and Cortisol suppression. Eur J Pharm Sci 1996; 4(6): 341–50Google Scholar
  269. 269.
    Ramakrishnan R, DuBois DC, Almon RR, et al. Fifth-generation model for corticosteroid pharmacodynamics: application to steady-state receptor down-regulation and enzyme induction patterns during seven-day continuous infusion of methyl-prednisolone in rats. J Pharmacokinet Pharmacodyn 2002; 29(1): 1–24PubMedGoogle Scholar
  270. 270.
    Hirano T, Oka K, Takeuchi H, et al. A comparison of prednisolone and methylprednisolone for renal transplantation. Clin Transplant 2000; 14 (4 Pt 1): 323–8PubMedGoogle Scholar
  271. 271.
    Tornatore KM, Logue G, Venuto RC, et al. Cortisol pharmacodynamics after methylprednisolone administration in young and elderly males. J Clin Pharmacol 1997; 37(4): 304–11PubMedGoogle Scholar
  272. 272.
    Stuck AE, Frey BM, Frey FJ. Kinetics of prednisolone and endogenous Cortisol suppression in the elderly. Clin Pharmacol Ther 1988; 43(4): 354–62PubMedGoogle Scholar
  273. 273.
    Sharma A, Ebling WF, Jusko WJ. Precursor-dependent indirect pharmacodynamic response model for tolerance and rebound phenomena. J Pharm Sci 1998; 87(12): 1577–84PubMedGoogle Scholar
  274. 274.
    Buttgereit F, da Silva JA, Boers M, et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 2002; 61(8): 718–22PubMedGoogle Scholar
  275. 275.
    Hayball PJ, Cosh DG, Ahern MJ, et al. High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics and clinical response. Eur J Clin Pharmacol 1992; 42(1): 85–8PubMedGoogle Scholar
  276. 276.
    Needs CJ, Smith M, Boutagy J, et al. Comparison of methylprednisolone (1g IV) with prednisolone (1g orally) in rheumatoid arthritis: a pharmacokinetic and clinical study. J Rheumatol 1988; 15: 224–8PubMedGoogle Scholar
  277. 277.
    Feduska NJ, Turcotte JG, Gikas PW, et al. Reversal of renal allograft rejection with intravenous methylprednisolone “pulse” therapy. J Surg Res 1972; 12(3): 208–15PubMedGoogle Scholar
  278. 278.
    August C, Schmid KW, Dietl KH, et al. Prognostic value of lymphocyte apoptosis in acute rejection of renal allografts. Transplantation 1999; 67(4): 581–5PubMedGoogle Scholar
  279. 279.
    Bolton WK, Sturgill BC. Methylprednisolone therapy for acute crescentic rapidly progressive glomerulonephritis. Am J Nephrol 1989; 9(5): 368–75PubMedGoogle Scholar
  280. 280.
    O’Neill Jr WM, Etheridge WB, Bloomer HA. High-dose corticosteroids: their use in treating idiopathic rapidly progressive glomerulonephritis. Arch Intern Med 1979; 139(5): 514–8PubMedGoogle Scholar
  281. 281.
    Vassalotti JA, Delgado FA, Whelton A. Atheroembolic renal disease. Am J Ther 1996; 3(7): 544–9PubMedGoogle Scholar
  282. 282.
    Santostefano M, Cocchi R, Fabbri A, et al. Steroid treatment of atheroembolic renal disease [abstract]. Nephrol Dial Transplant 2003; 18 Suppl. 4: 622Google Scholar
  283. 283.
    Barile LA, Jara LJ, Medina-Rodriguez F, et al. Pulmonary hemorrhage in systemic lupus erythematosus. Lupus 1997; 6(5): 445–8PubMedGoogle Scholar
  284. 284.
    Leatherman JW, Davies SF, Hoidal JR. Alveolar hemorrhage syndromes: diffuse microvascular lung hemorrhage in immune and idiopathic disorders. Medicine (Baltimore) 1984; 63(6): 343–61Google Scholar
  285. 285.
    Metcalf JP, Rennard SI, Reed EC, et al. Corticosteroids as adjunctive therapy for diffuse alveolar hemorrhage associated with bone marrow transplantation. University of Nebraska Medical Center Bone Marrow Transplant Group. Am J Med 1994; 96(4): 327–34PubMedGoogle Scholar
  286. 286.
    Bracken MB. Steroids for acute spinal cord injury. Cochrane Database Syst Rev 2002; (3): CD001046PubMedGoogle Scholar
  287. 287.
    de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347(20): 1549–56PubMedGoogle Scholar
  288. 288.
    Balis FM, Lester CM, Chrousos GP, et al. Differences in cerebrospinal fluid penetration of corticosteroids: possible relationship to the prevention of meningeal leukemia. J Clin Oncol 1987; 5(2): 202–7PubMedGoogle Scholar
  289. 289.
    Chatham WW, Kimberly RP. Treatment of lupus with corticosteroids. Lupus 2001; 10(3): 140–7PubMedGoogle Scholar
  290. 290.
    Illei GG, Austin HA, Crane M, et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 2001; 135(4): 248–57PubMedGoogle Scholar
  291. 291.
    Bellomio V, Spindler A, Lucero E, et al. Systemic lupus erythematosus: mortality and survival in argentina: a multicenter study. Lupus 2000; 9(5): 377–81PubMedGoogle Scholar
  292. 292.
    Cathcart ES, Idelson BA, Scheinberg MA, et al. Beneficial effects of methylprednisolone “pulse” therapy in diffuse proliferative lupus nephritis. Lancet 1976; I(7952): 163–6Google Scholar
  293. 293.
    Honma M, Ichikawa Y, Akizuki M, et al. Double blind trial of pulse methylprednisolone versus conventional oral prednisolone in lupus nephritis [in Japanese]. Ryumachi 1994; 34(3): 616–27PubMedGoogle Scholar
  294. 294.
    Barron KS, Person DA, Brewer Jr EJ, et al. Pulse methylprednisolone therapy in diffuse proliferative lupus nephritis. J Pediatr 1982; 101(1): 137–41PubMedGoogle Scholar
  295. 295.
    Rose GM, Cole BR, Robson AM. The treatment of severe glomerulopathies in children using high dose intravenous methylprednisolone pulses. Am J Kidney Dis 1981; 1(3): 148–56PubMedGoogle Scholar
  296. 296.
    Eyanson S, Passo MH, Aldo-Benson MA, et al. Methylprednisolone pulse therapy for nonrenal lupus erythematosus. Ann Rheum Dis 1980; 39(4): 377–80PubMedGoogle Scholar
  297. 297.
    Pozzi C, Bolasco PG, Fogazzi GB, et al. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet 1999; 353(9156): 883–7PubMedGoogle Scholar
  298. 298.
    Murnaghan K, Vasmant D, Bensman A. Pulse methylprednisolone therapy in severe idiopathic childhood nephrotic syndrome. Acta Paediatr Scand 1984; 73(6): 733–9PubMedGoogle Scholar
  299. 299.
    Gertz MA, Garton JP, Greipp PR, et al. A phase II study of high-dose methylprednisolone in refractory or relapsed multiple myeloma. Leukemia 1995; 9(12): 2115–8PubMedGoogle Scholar
  300. 300.
    Wong P, Cuello C, Bertouch JV, et al. The effects of pulse methylprednisolone on matrix metalloproteinase and tissue inhibitor of metalloproteinase-1 expression in rheumatoid arthritis. Rheumatology (Oxf) 2000; 39(10): 1067–73Google Scholar
  301. 301.
    Kirwan JR. The effect of glucocorticoids on joint destruction in rheumatoid arthritis: the arthritis and rheumatism council lowdose glucocorticoid study group. N Engl J Med 1995; 333(3): 142–6PubMedGoogle Scholar
  302. 302.
    Engel T, Dirksen A, Frolund L, et al. Methylprednisolone pulse therapy in acute severe asthma: a randomized, double-blind study. Allergy 1990; 45(3): 224–30PubMedGoogle Scholar
  303. 303.
    Bowler SD, Mitchell CA, Armstrong JG. Corticosteroids in acute severe asthma: effectiveness of low doses. Thorax 1992; 47(8): 584–7PubMedGoogle Scholar
  304. 304.
    Greos LS, Vichyanond P, Bloedow DC, et al. Methylprednisolone achieves greater concentrations in the lung than prednisolone: a pharmacokinetic analysis. Am Rev Respir Dis 1991; 144 (3 Pt 1): 586–92PubMedGoogle Scholar
  305. 305.
    MacLaren R, Jung R. Stress-dose corticosteroid therapy for sepsis and acute lung injury or acute respiratory distress syndrome in critically ill adults. Pharmacotherapy 2002; 22(9): 1140–56PubMedGoogle Scholar
  306. 306.
    Luce JM, Montgomery AB, Marks JD, et al. Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with septic shock. Am Rev Respir Dis 1988; 138(1): 62–8PubMedGoogle Scholar
  307. 307.
    Bernard GR, Luce JM, Sprung CL, et al. High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med 1987; 317(25): 1565–70PubMedGoogle Scholar
  308. 308.
    Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288(7): 862–71PubMedGoogle Scholar
  309. 309.
    Meduri GU, Headley AS, Golden E, et al. Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA 1998; 280(2): 159–65PubMedGoogle Scholar
  310. 310.
    van Vollenhoven RF. Corticosteroids in rheumatic disease: understanding their effects is key to their use. Postgrad Med 1998; 103(2): 137–42PubMedGoogle Scholar
  311. 311.
    Curtis JJ, Galla JH, Woodford SY, et al. Comparison of daily and alternate-day prednisone during chronic maintenance therapy: a controlled crossover study. Am J Kidney Dis 1981; 1(3): 166–71PubMedGoogle Scholar
  312. 312.
    Hunder GG, Sheps SG, Allen GL, et al. Daily and alternate-day corticosteroid regimens in treatment of giant cell arteritis: comparison in a prospective study. Ann Intern Med 1975; 82(5): 613–8PubMedGoogle Scholar
  313. 313.
    Groves RW, Toms GC, Houghton BJ, et al. Corticosteroid replacement therapy: twice or thrice daily? J R Soc Med 1988; 81(9): 514–6PubMedGoogle Scholar
  314. 314.
    Malo JL, Cartier A, Merland N, et al. Four-times-a-day dosing frequency is better than a twice-a-day regimen in subjects requiring a high-dose inhaled steroid, budesonide, to control moderate to severe asthma. Am Rev Respir Dis 1989; 140(3): 624–8PubMedGoogle Scholar
  315. 315.
    Keller F, Hemmen T, Schoneshofer M, et al. Pharmacokinetics of methylprednisolone and rejection episodes in kidney transplant patients. Transplantation 1995; 60(4): 330–3PubMedGoogle Scholar
  316. 316.
    Briggs WA, Gimenez LF, Samaniego-Picota M, et al. Relationship between lymphocyte and clinical steroid responsiveness in focal segmental glomerulosclerosis. J Clin Pharmacol 2000; 40(2): 115–23PubMedGoogle Scholar
  317. 317.
    Pollak R, Dumble LJ, Lazda VA, et al. Utility of an in vitro immunoassay to guide immunosuppressive therapy. Transplant Proc 1991; 23 (1 Pt 2): 1113–4PubMedGoogle Scholar
  318. 318.
    Langhoff E, Ladefoged J. The impact of high lymphocyte sensitivity to glucocorticoids on kidney graft survival in patients treated with azathioprine and cyclosporine. Transplantation 1987; 43(3): 380–4PubMedGoogle Scholar
  319. 319.
    Poznansky MC, Gordon AC, Douglas JG, et al. Resistance to methylprednisolone in cultures of blood mononuclear cells from glucocorticoid-resistant asthmatic patients. Clin Sci (Lond) 1984; 67(6): 639–45Google Scholar
  320. 320.
    Kirkham BW, Corkill MM, Davison SC, et al. Response to glucocorticoid treatment in rheumatoid arthritis: in vitro cell mediated immune assay predicts in vivo responses. J Rheumatol 1991; 18(6): 821–5PubMedGoogle Scholar
  321. 321.
    Liddle GW. Clinical pharmacology of the anti-inflammatory steroids. Clin Pharmacol Ther 1961; 2(5): 615–35PubMedGoogle Scholar
  322. 322.
    Zellner D, Frankewitsch T, Simon S, et al. Statistical analysis of heterogeneous pharmacokinetic data from the literature. Eur J Clin Chem Clin Biochem 1996; 34(7): 585–9PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • David Czock
    • 1
  • Frieder Keller
    • 1
    Email author
  • Franz Maximilian Rasche
    • 1
  • Ulla Häussler
    • 1
  1. 1.Division of NephrologyUniversity Hospital UlmUlmGermany

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