Clinical Pharmacokinetics

, Volume 19, Issue 2, pp 126–146 | Cite as

Clinical Pharmacokinetics of Prednisone and Prednisolone

  • Brigitte M. Frey
  • Felix J. Frey
Drug Disposition


The growth of knowledge in the field of the pharmacokinetics of prednisolone/prednisone has been slow for several reasons. First, convenient and specific methods for measuring these steroids only became available with the development of high performance liquid Chromatographic methods. Secondly, prednisolone is nonlinearly bound to transcortin and albumin: since the unbound concentrations of prednisolone are biologically relevant, it was necessary to determine the free fraction in each plasma sample. Thirdly, due to the short half-life of prednisolone no steady-state is achieved, and therefore area under the concentration-time curve needed to be determined in all studies. Fourthly, prednisolone and prednisone are interconvertible and prednisolone is given intravenously as an ester prodrug, features which created controversies about the correct interpretation of pharmacokinetic results. Finally, the total body clearances of total and (to a lesser degree) of unbound prednisolone increase with increasing concentrations of prednisolone. Therefore, in order to compare pharmacokinetic results between different subjects, standardised doses had to be administered.

The investigations performed so far have revealed that: (1) the dose-dependent pharmacokinetics partly explain the clinical observation that an alternate-day regimen with prednisone yields fewer biological effects; (2) the interconversion of prednisone into prednisolone is not a limiting factor, even in patients with severely impaired liver function; (3) hypoproteinaemia per se does not cause increased unbound concentrations of prednisolone in vivo; (4) patients with liver failure, renal failure or a renal transplant, subjects older than 65 years, women on estrogen-containing oral contraceptive steroids or subjects taking ketoconazole have increased unbound concentrations of prednisolone - whereas hyperthyroid patients, some patients with Crohn’s disease, subjects taking microsomal liver enzyme-inducing agents or patients on intravenous prednisolone phthalate (instead of prednisolone phosphate) or on some brands of enteric coated prednisolone tablets have decreased concentrations of prednisolone. The biological relevance of the altered pharmacokinetics is supported in part by altered clinical effects and altered effects on cellular immunofunctions.


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  1. Al-Habet S, Rogers HJ. Pharmacokinetics of intravenous and oral prednisolone. British Journal of Clinical Pharmacology 10: 503–508, 1980PubMedCrossRefGoogle Scholar
  2. Angeli A, Frajria R, De Paoli R, Fonzo D, Ceresa F. Diurnal variation of prednisolone binding to serum corticosteroidbinding globulin in man. Clinical Pharmacology and Therapeutics 23: 47–53, 1978PubMedGoogle Scholar
  3. Araki Y, Yokota O, Kato T, Kashima M, Miyazaki T. Dynamics of synthetic corticosteroids in man. In Pincus et al. (Eds) Steroid dynamics, pp. 463–480, Academic Press, 1966Google Scholar
  4. Bartoszek M, Brenner AM, Szefler SJ. Prednisolone and methylprednisolone kinetics in children receiving anticonvulsam therapy. Clinical Pharmacology and Therapeutics 42: 424–432, 1987PubMedCrossRefGoogle Scholar
  5. Behm HL, Wagner JG. Errors in interpretation of data from equilibrium dialysis protein binding experiments. Research Communications in Chemical Pathology and Pharmacology 26: 145–160, 1979PubMedGoogle Scholar
  6. Benet LZ, Galeazzi RL. Noncompartmental determination of the steady-state volume of distribution. Journal of Pharmaceutical Sciences 68: 1071–1074, 1979PubMedCrossRefGoogle Scholar
  7. Bergrem H. The influence of uremia on pharmacokinetics and protein binding of prednisolone. Acta Medica Scandinavica 213: 333–337, 1983aPubMedCrossRefGoogle Scholar
  8. Bergrem H. Pharmacokinetics and protein binding of prednisolone in patients with nephrotic syndrome and patients undergoing hemodialysis. Kidney International 23: 876–881, 1983bPubMedCrossRefGoogle Scholar
  9. Bergrem H, Groitum P, Rugstad HE. Pharmacokinetics and protein binding of prednisolone after oral and intravenous administration. European Journal of Clinical Pharmacology 24: 415–419, 1983PubMedCrossRefGoogle Scholar
  10. Bergrem H, Jervell J, Flatmark A. Prednisolone pharmacokinetics in cushingoid and non-cushingoid kidney transplant patients. Kidney International 27: 459–464, 1985PubMedCrossRefGoogle Scholar
  11. Bergrem H, Opedal I. Bioavailability of prednisolone in patients with intestinal malabsorption: the importance of measuring serum protein binding. Scandinavian Journal of Gastroenterology 18: 545–549, 1983PubMedCrossRefGoogle Scholar
  12. Bergrem H, Refvem OK. Altered prednisolone pharmacokinetics in patients treated with rifampicin. Acta Medica Scandinavica 213: 339–343, 1983PubMedCrossRefGoogle Scholar
  13. Boekenoogen SJ, Szefler SJ, Jusko WJ. Prednisolone disposition and protein binding in oral contraceptive users. Journal of Clinical Endocrinology and Metabolism 56: 702–709, 1983PubMedCrossRefGoogle Scholar
  14. Boudinot FD, Jusko WJ. Plasma protein binding interaction of prednisone and prednisolone. Journal of Steroid Biochemistry 21: 337–339, 1984PubMedCrossRefGoogle Scholar
  15. Brion N, Pibarot ML, Atienza P, Robin P, Carbon C. Comparative serum pharmacokinetics of prednisone and prednisolone methylsulfobenzoate after oral administration. Presse Medicale 17: 569–571, 1988Google Scholar
  16. Brooks PM, Buchanan WW, Grove M, Downie WW. Effects of enzyme induction on metabolism of prednisolone. Annals of Rheumatic Diseases 35: 339–343, 1976CrossRefGoogle Scholar
  17. Brown MW, Maldonado AL, Meredith CG, Speeg Jr KV. Effect of ketoconazole on hepatic oxidative drug metabolism. Clinical Pharmacology and Therapeutics 37: 290–297, 1985PubMedCrossRefGoogle Scholar
  18. Buffington GA, Dominguez JH, Piering WF, Hebert LA, Kauffman HM, et al. Interaction of rifampicin and glucocorticoids. Adverse effect on renal allograft function. Journal of the American Medical Association 236: 1958–1960, 1976PubMedCrossRefGoogle Scholar
  19. Bührer M, Frey BM, Frey FJ. Availability of prednisolone in csf from different iv prednisolone prodrugs. Clinical Pharmacology and Therapeutics 45: 166, 1989Google Scholar
  20. Caspi E, Pechet MM. The metabolism of l-dehydro-steroids in man: isolation of 6 urinary products following the administration of 11β, 17α, 21-trihydroxy-l, 4-pregnadiene-3, 20-dione. Archives of Biochemistry and Biophysics 68: 236–237, 1957PubMedCrossRefGoogle Scholar
  21. Cunningham C, Gavin M, Whiting D. Serum cyclosporine levels, hepatic drug metabolism and renal tubulotoxicity. Biochemical Pharmacology 33: 2857–2861, 1984PubMedCrossRefGoogle Scholar
  22. Curtis JJ, Galla JH, Woodford SY, Saykaly RJ, Luke RH. Comparison of daily and alternate-day prednisone during chronic maintenance therapy: a controlled cross-over study. American Journal of Kidney Diseases 1: 166–171, 1981PubMedGoogle Scholar
  23. Davis M, Williams R, Chakraborty J, English J, Marks V, et al. Prednisone or prednisolone for the treatment of chronic active hepatitis? A comparison of plasma availability. British Journal of Clinical Pharmacology 5: 501–505, 1978PubMedCrossRefGoogle Scholar
  24. Dazord A, Saez J, Bertrand J. Metabolic clearance rates and interconversion of cortisol and cortisone. Journal of Clinical Endocrinology and Metabolism 35: 24–34, 1971CrossRefGoogle Scholar
  25. Derendorf H, Rohdewald P, Möllmann H, Rehder J, Barth J, et al. Pharmacokinetics of prednisolone after high doses of prednisolone hemisuccinate. Biopharmaceutics and Drug Disposition 6: 423–432, 1985CrossRefGoogle Scholar
  26. Ebling WF, Jusko WJ. The determination of essential clearance, volume, and residence time parameters of recirculating metabolic systems: the reversible metabolism of methylprednisolone and methylprednisone in rabbits. Journal of Pharmacokinetics and Biopharmaceutics 14: 557–599, 1985Google Scholar
  27. Elliott PR, Powell-Tuck J, Gillespie PE, Laidlow JM, LennardJones JE, et al. Prednisolone absorption in acute colitis. Gut 21: 49–51, 1980PubMedCrossRefGoogle Scholar
  28. English J, Dunne M, Marks V. Diurnal variation in prednisolone kinetics. Clinical Pharmacology and Therapeutics 33: 381–385, 1983PubMedCrossRefGoogle Scholar
  29. Ferry JJ, Wagner JG. The nonlinear pharmacokinetics of prednisone and prednisolone: II. Plasma protein binding of prednisone and prednisolone in rabbit and human plasma. Biopharmaceutics and Drug Disposition 8: 261–272, 1987CrossRefGoogle Scholar
  30. Frey BM, Brandenberger AW, Frey FJ, Widmer HR. Systemische Verfügbarkeit von Prednisolon nach oral verabreichtem Prednison. Pharmaceutica Acta Helvetiae 11: 301–309, 1984cGoogle Scholar
  31. Frey BM, Frey FJ. Simultaneous measurement of prednisone, prednisolone and 6β-hydroxyprednisolone in urine by high performance liquid chromatography coupled with a radioactivity monitor. Journal of Chromatography 229: 283–292, 1982PubMedCrossRefGoogle Scholar
  32. Frey BM, Frey FJ. Phenytoin modulates the pharmacokinetics of prednisolone and the pharmacodynamics of prednisolone as assessed by the inhibition of the mixed lymphocyte reaction in humans. European Journal of Clinical Investigation 14: 1–6, 1984PubMedCrossRefGoogle Scholar
  33. Frey BM, Frey FJ. The effect of altered prednisolone kinetics in patients with the nephrotic syndrome and in women taking oral contraceptive steroids on human mixed lymphocyte cultures. Journal of Clinical Endocrinology and Metabolism 60: 361–369, 1985PubMedCrossRefGoogle Scholar
  34. Frey BM, Frey FJ, Benet LZ, Cochrum KC. Modification of the mixed lymphocyte reaction for pharmacokinetic assessment of immunosuppressive activity in human plasma. International Journal of Immunopharmacology 2: 129–134, 1980CrossRefGoogle Scholar
  35. Frey BM, Frey FJ, Holford N, Lozada F, Benet LZ. Prednisolone pharmacodynamics assessed by inhibition of the mixed lymphocyte reaction. Transplantation 6: 578–584, 1982CrossRefGoogle Scholar
  36. Frey BM, Hugentobler T, Bührer M, Frey FJ. Transcortinkonzentrationen im Plasma von Normalpersonen und Patienten mit Nierendoder Lebererkrankungen. Klinische Wochenschrift 62: 936–938, 1984aPubMedCrossRefGoogle Scholar
  37. Frey BM, Schaad HJ, Frey FJ. Pharmacokinetic interaction of contraceptive steroids with prednisone and prednisolone. European Journal of Clinical Pharmacology 26: 505–511, 1984bPubMedCrossRefGoogle Scholar
  38. Frey BM, Seeberger M, Frey FJ. Pharmacokinetics of 3 different prednisolone prodrugs: evidence for therapeutic inequivalence in renal transplant patients with rejection. Transplantation 39: 270–281, 1985PubMedCrossRefGoogle Scholar
  39. Frey BM, Walker C, Frey FJ, de Weck AL. Pharmacokinetics and pharmacodynamics of 3 different prednisolone prodrugs: effect on circulating lymphocyte subsets and function. Journal of Immunology 133: 2479–2487, 1984dGoogle Scholar
  40. Frey FJ. Kinetics and dynamics of prednisolone. Endocrine Reviews 8: 453–473, 1987PubMedCrossRefGoogle Scholar
  41. Frey FJ, Amend Jr WJC, Lozada F, Frey BM, Benet LZ. Endogenous hydrocortisone, a possible factor contributing to the genesis of cushingoid habitus in patients on prednisone. Journal of Clinical Endocrinology and Metabolism 53: 1076–1080, 1981aPubMedCrossRefGoogle Scholar
  42. Frey FJ, Amend JW, Lozada F, Frey BM, Holford N, et al. Pharmacokinetics of prednisolone and endogenous hydrocortisone levels in cushingoid and non-cushingoid patients. European Journal of Clinical Pharmacology 21: 235–243, 1981bPubMedCrossRefGoogle Scholar
  43. Frey FJ, Frey BM. Altered prednisolone kinetics in patients with the nephrotic syndrome. Nephron 32: 45–48, 1982PubMedCrossRefGoogle Scholar
  44. Frey FJ, Frey BM. Urinary 6β-hydroxyprednisolone excretion indicates enhanced prednisolone catabolism. Journal of Laboratory and Clinical Medicine 101: 593–604, 1983PubMedGoogle Scholar
  45. Frey FJ, Frey BM. Altered plasma protein-binding of prednisolone in patients with the nephrotic syndrome. American Journal of Kidney Diseases 3: 339–342, 1984PubMedGoogle Scholar
  46. Frey FJ, Frey BM, Benet LZ. Liquid-chromatographic measurements of endogenous and exogenous glucocorticoids in plasma. Clinical Chemistry 25: 1944–1947, 1979PubMedGoogle Scholar
  47. Frey FJ, Frey BM, Greither A, Benet LZ. Prednisolone clearance at steady state in dogs. Journal of Pharmacology and Experimental Therapeutics 215: 287–291, 1980PubMedGoogle Scholar
  48. Frey FJ, Frey BM, Schnetzer A, Horber FF. Evidence that cyclosporine A does not affect the metabolism of prednisolone after renal transplantation. Transplantation 43: 494–498, 1987PubMedCrossRefGoogle Scholar
  49. Frey FJ, Gambertoglio JG, Frey BM, Benet LZ, Amend WJC. Nonlinear plasma protein binding and hemodialysis clearance. European Journal of Clinical Pharmacology 23: 65–74, 1982PubMedCrossRefGoogle Scholar
  50. Frey FJ, Horber FF, Frey BM. Altered metabolism and decreased efficacy of prednisolone and prednisone in hyperthyroid patients. Clinical Pharmacology and Therapeutics 44: 510–521, 1988PubMedCrossRefGoogle Scholar
  51. Frey FJ, Lozada F, Guentert T, Frey BM. A single dose of azathioprine does not affect the pharmacokinetics of prednisolone. European Journal of Clinical Pharmacology 19: 209–212, 1981cPubMedCrossRefGoogle Scholar
  52. Frey FJ, Rügsegger MK, Frey BM. The dose-dependent systemic availability of prednisone, one reason for the reduced biological effect of alternate-day prednisone. British Journal of Clinical Pharmacology 21: 183–189, 1986PubMedCrossRefGoogle Scholar
  53. Frey FJ, Schaad HJ, Renner EL, Horber FF, Frey BM, et al. Liver function in stable renal transplant patients. Hepatology 9: 606–613, 1989PubMedCrossRefGoogle Scholar
  54. Galla JH, Curtis JJ, Woodford SY, Rees ED, Somes GW, et al. Effect of prednisone dose spacing on plasma lipids. Journal of Laboratory and Clinical Medicine 95: 801–807, 1980PubMedGoogle Scholar
  55. Gambertoglio JG, Amend Jr WJC, Benet LZ. Pharmacokinetics and bioavailability of prednisone and prednisolone in healthy volunteers and patients: a review. Journal of Pharmacokinetics and Biopharmaceutics 8: 1–52, 1980aPubMedCrossRefGoogle Scholar
  56. Gambertoglio JG, Frey FJ, Holford NHG, Birnbaum JL, Lizak PS, et al. Prednisone and prednisolone bioavailability in renal transplant patients. Kidney International 21: 621–626, 1982PubMedCrossRefGoogle Scholar
  57. Gambertoglio JG, Holford NHG, Kapusnik JE, Nishikawa RA, Lizak P, et al. Disposition of total and unbound prednisolone in renal transplant patients receiving anticonvulsants. Kidney International 25: 119–123, 1984bPubMedCrossRefGoogle Scholar
  58. Gambertoglio JG, Holford NHG, Lizak PS, Birnbaum JL, Salvatierra O, et al. The absence of effect of azathioprine on prednisolone pharmacokinetics following maintenance prednisone doses in kidney transplant patients. American Journal of Kidney Diseases 3: 425–429, 1984aPubMedGoogle Scholar
  59. Gambertoglio JG, Romac DR, Yong CL, Birnbaum J, Lizak P, et al. Lack of effect of sucralfate on prednisone bioavailability. American Journal of Gastroenterology 82: 12–15, 1987Google Scholar
  60. Gambertoglio JG, Vincenti F, Feduska NJ, Birnbaum J, Salvatierra Jr O, et al. Prednisolone disposition in cushingoid and noncushingoid kidney transplant patients. Journal of Clinical Endocrinology and Metabolism 51: 561–565, 1980bPubMedCrossRefGoogle Scholar
  61. Greenberger PA, Chow MJ, Atkinson Jr AJ, Ambre JJ, Patterson R. Comparison of prednisolone kinetics in patients receiving daily or alternate-day prednisone for asthma. Clinical Pharmacology and Therapeutics 39: 163–168, 1986PubMedCrossRefGoogle Scholar
  62. Gustafsson JA, Carlstedt-Duke J, Poellinger L, Okret S, Wikström AC, et al. Biochemistry, molecular biology and physiology of the glucocorticoid receptor. Endocrine Reviews 8: 185–234, 1987PubMedCrossRefGoogle Scholar
  63. Gustavson LE, Benet LZ. The macromolecular binding of prednisone in plasma of healthy volunteers including pregnant women and oral contraceptive users. Journal of Pharmacokinetics and Biopharmaceutics 13: 561–569, 1985PubMedCrossRefGoogle Scholar
  64. Gustavson LE, Legier UF, Benet LZ. Impairment of prednisolone disposition in women taking oral contraceptives or conjugated estrogens. Journal of Clinical Endocrinology and Metabolism 62: 234–237, 1986PubMedCrossRefGoogle Scholar
  65. Henderson RG, Wheatley T, English J, Chakraborty J, Marks V. Variation in plasma prednisolone concentrations in renal transplant recipients given enteric-coated prednisolone. British Medical Journal 1: 1534–1536, 1979PubMedCrossRefGoogle Scholar
  66. Hendrickse W, Mickierman J, Pickup M, Lowe J. Rifampicin-induced non-responsiveness to corticosteroid treatment in nephrotic syndrome. British Medical Journal 1: 306, 1979PubMedCrossRefGoogle Scholar
  67. Hunder GG, Sheps SG, Allen GL, Joyce JW. Daily and alternateday corticosteroid regimens in treatment of giant cell arteritis: comparison in a prospective study. Annals of Internal Medicine 82: 613–618, 1975PubMedGoogle Scholar
  68. Jenkins JS, Sampson PA. Conversion of cortisone to cortisol and prednisone to prednisolone. British Medical Journal 2: 205–207, 1967PubMedCrossRefGoogle Scholar
  69. Khalafallah N, Jusko WJ. Tissue distribution of prednisolone in the rabbit. Journal of Pharmacology and Experimental Therapeutics 229: 719–725, 1984PubMedGoogle Scholar
  70. Klotz U, Avant GR, Hoyumpa A. The effects of age and liver disease on the disposition and elimination of diazepam in adult man. Journal of Clinical Investigation 55: 347–359, 1975PubMedCrossRefGoogle Scholar
  71. Kort WJ, Weijma IM, Westbroek DL. Reductive effect of phenobarbital on graft survival in prednisolone-trealed rats. European Surgical Research 11: 317–324, 1979CrossRefGoogle Scholar
  72. Kozower M, Veatch L, Kaplan MM. Decreased clearance of prednisolone, a factor in the development of corticosteroid side effect. Journal of Clinical Endocrinology and Metabolism 38: 407–412, 1974PubMedCrossRefGoogle Scholar
  73. Krauss JW, Desmond PV, Marshall JP. The effects of aging and liver disease on the disposition of lorazepam in man. Clinical Pharmacology and Therapeutics 24: 411–419, 1978Google Scholar
  74. Langhoff E, Madsen S, Hvidberg E. Inhibition of prednisolone metabolism by cyclosporine in kidney-transplanted patients. Transplantation 39: 107–109, 1985PubMedCrossRefGoogle Scholar
  75. Lee DA, Taylor GM, James VH, Walker G. Plasma prednisolone levels and adrenocortical responsiveness after administration of prednisolone-21-phosphate as a retention enema. Gut 20: 349–355, 1979PubMedCrossRefGoogle Scholar
  76. Legier UF, Enhanced prednisolone elimination: a possible cause for failure of glucocorticoid therapy in Graves ophthalmopathy. Hormone and Metabolic Research 19: 168–170, 1987CrossRefGoogle Scholar
  77. Legier UF. Impairment of prednisolone disposition in patients with Graves disease taking methimazole. Journal of Clinical Endocrinology and Metabolism 66: 221–223, 1988CrossRefGoogle Scholar
  78. Legier UF, Benet LZ. Marked alterations in dose-dependent prednisolone kinetics in women taking oral contraceptives. Clinical Pharmacology and Therapeutics 39: 425–429, 1986aCrossRefGoogle Scholar
  79. Legier UF, Benet LZ. The effect of prednisone and hydrocortisone on the plasma protein binding of prednisolone in man. European Journal of Clinical Pharmacology 30: 51–55, 1986bCrossRefGoogle Scholar
  80. Legier UF, Frey FJ, Benet LZ. Prednisolone clearance at steady state in humans. Journal of Clinical Endocrinology and Metabolism 55: 762–767, 1982CrossRefGoogle Scholar
  81. Lewis GP, Jusko WJ, Burke CW, Graves L. Prednisone side-effects and serum protein levels. Lancet 2: 778–781, 1971PubMedCrossRefGoogle Scholar
  82. Loose DS, Kan PB, Hirs MA, Marcus RA, Feldman D. Ketoconazole blocks adrenal steroidogenesis by inhibiting cytochrome P-450-dependent enzymes. Journal of Clinical Investigation 71: 1495–1499, 1983PubMedCrossRefGoogle Scholar
  83. Ludwig EA, Slaughter RL, Savliwala M, Brass C, Jusko WJ. Ketoconazole effects on prednisolone pharmacokinetics and cortisol suppression. Drug Intelligence and Clinical Pharmacy 21: 5A–6A, 1987Google Scholar
  84. Madsbad S, Bjerregaard B, Henriksen JH, Kuhl E, Kehlet H. Impaired conversion of prednisone to prednisolone in patients with liver cirrhosis. Gut 21: 52–56, 1980PubMedCrossRefGoogle Scholar
  85. McAllister WAC, Mitchell DM, Collins JV. Prednisolone pharmacokinetics compared between night and day in asthmatic and normal subjects. British Journal of Clinical Pharmacology 11: 303–404, 1981PubMedCrossRefGoogle Scholar
  86. McAllister WAC, Thompson PJ, Al-Habet SM, Rogers HJ. Rifampicin reduces effectiveness and bioavailability of prednisolone. British Medical Journal 286: 923–925, 1983PubMedCrossRefGoogle Scholar
  87. McGuire Jr JS, Tomkins GM. The effects of thyroxin administration on the enzymic reduction of Δ4-3-ketosteroids. Journal of Biological Chemistry 234: 791–794, 1959PubMedGoogle Scholar
  88. McIntyre PB, Macrae FA, Berghouse L, English J, Lennard-Jones JE. Therapeutic benefits from a poorly absorbed prednisolone enema in distal colitis. Gut 26: 822–824, 1985PubMedCrossRefGoogle Scholar
  89. Meffin PJ, Brooks PM, Sallustio BC. Alterations in prednisolone disposition as a result of time administration, gender and dose. British Journal of Clinical Pharmacology 17: 395–404, 1984bPubMedCrossRefGoogle Scholar
  90. Meffin PJ, Sallustio BC, Purdie YJ, Robson RA, Wing LMH, et al. Cortisol does not inhibit prednisolone clearance. British Journal of Clinical Pharmacology 20: 414–416, 1985PubMedCrossRefGoogle Scholar
  91. Meffin PJ, Wing LMH, Sallustio BC, Brooks PM. Alterations in prednisolone disposition as a result of oral contraceptive use and dose. British Journal of Clinical Pharmacology 17: 655–664, 1984aPubMedCrossRefGoogle Scholar
  92. Meikle AW, Weed JA, Tyler FH. Kinetics and interconversion of prednisolone and prednisone studied with new radioimmunoassays. Journal of Clinical Endocrinology and Metabolism 41: 717–721, 1975PubMedCrossRefGoogle Scholar
  93. Milsap RL, George DE, Szefler SJ, Murray KA, Lebenthal E, et al. Effect of inflammatory bowel disease on absorption and disposition of prednisolone. Digestive Diseases Sciences 28: 161–168, 1983CrossRefGoogle Scholar
  94. Milsap RL, Jusko WJ. Binding of prednisolone to α1-acid-glycoprotein. Journal of Steroid Biochemistry 18: 191–194, 1983PubMedCrossRefGoogle Scholar
  95. Milsap RL, Plaisance KI, Jusko WJ. Prednisolone disposition in obese men. Clinical Pharmacology and Therapeutics 36: 824–831, 1984PubMedCrossRefGoogle Scholar
  96. Morrison PJ, Rogers HJ, Bradbrook ID, Parsons C. Concurrent administration of cimetidine and enteric-coated prednisolone: effect on plasma levels of prednisolone. British Journal of Clinical Pharmacology 10: 87–89, 1980PubMedCrossRefGoogle Scholar
  97. Neimegeers CJ, Levron JC, Awduters F. Inhibition and induction of microsomal enzymes in rat: a comparative study of four antimycotics: miconazole, econazole, clotrimazole and ketoconazole. Archives Internationales de Pharmacodynamie et de Thérapie 251: 26–28, 1981Google Scholar
  98. Nelson DH, Tanney H, Mestman G, Gieschen VW, Wilson LD. Potentiation of the biologic effect of administered cortisol by estrogen treatment. Journal of Clinical Endocrinology and Metabolism 23: 261–265, 1963PubMedCrossRefGoogle Scholar
  99. Odds FO, Webster CE. Effects of azole antifungals in vitro on host/parasite interactions relevant to Candida infections. Journal of Antimicrobial Agents and Chemotherapeutics 22: 173–181, 1988Google Scholar
  100. Oest L, Björkhem I, von Bahr C. Clinical value of assessing prednisolone pharmacokinetics before and after renal transplantation. European Journal of Clinical Pharmacology 26: 363–369, 1984CrossRefGoogle Scholar
  101. Oest L, Klintmalm G, Ringden O. Mutual interaction between prednisolone and cyclosporine in renal transplant patients. Transpianation Proceedings 17: 1252–1254, 1985Google Scholar
  102. Ogawa K, Sueda K, Matsui N. The effect of cortisol, progesterone and transcortin on phytohemagglutinin-stimulated human blood mononuclear cells and their interplay. Journal of Clinical Endocrinology and Metabolism 56: 121–126, 1983PubMedCrossRefGoogle Scholar
  103. Olivesi A. Non-absorption of enteric-coated prednisolone. Normal absorption of non-enteric-coated prednisolone in a patient with Crohn’s disease and massive intestinal resection. Therapie 40: 5–7, 1985PubMedGoogle Scholar
  104. Oosterhuis B, Ten Berge RJM, Sauerwein HP, Enden E, Schellekens PTA, et al. Pharmacokinetic-pharmacodynamic modelling of prednisolone-induced lymphocytopenia in man. Journal of Pharmacology and Experimental Therapeutics 229: 539–546, 1984PubMedGoogle Scholar
  105. Oosterhuis B, Ten Berge IJM, Schellekens PTA, Koopmans RP, Van Boxtel CJ. Prednisolone concentration-effect relations in humans and the influence of plasma hydrocortisone. Journal of Pharmacology and Experimental Therapeutics 239: 919–926, 1986PubMedGoogle Scholar
  106. Oostenhuis B, Ten Berge IJ, Schellekens PT, Van Boxtel CJ. Concentration-dependent effects of prednisolone on lymphocyte subsets and mixed lymphocyte culture in humans. Journal of Pharmacology and Experimental Therapeutics 243: 716–722, 1987Google Scholar
  107. Ortiz de Montellano RR, Kunze KL, Yost GS, Mico BA. Selfcatalyzed destruction of cytochrome P-450: covalent binding of ethynyl sterols to prosthetic heme. Proceedings of the National Academy of Sciences of the United States of America 76: 746–749, 1979PubMedCrossRefGoogle Scholar
  108. Pessayre D, Konstantinova-Mitcheva M, Descatoire V, Cobert B, Wandscheer J-C, et al. Hypoactivity of cytochrome P-450 after triacetyloleandomycin administration. Biochemical Pharmacology 30: 559–563, 1981PubMedCrossRefGoogle Scholar
  109. Petereit LB, Meikle AW, Effectiveness of prednisolone during phenytoin therapy. Clinical Pharmacology and Therapeutics 22: 912–916, 1977PubMedGoogle Scholar
  110. Pickup ME. Clinical pharmacokinetics of prednisone and prednisolone. Clinical Pharmacokinetics 4: 111–128, 1979PubMedCrossRefGoogle Scholar
  111. Pickup ME, Lowe JR, Leatham PA, Rhind VM, Wright V, et al. Dose dependent pharmacokinetics of prednisolone. European Journal of Clinical Pharmacology 12: 213–219, 1977PubMedCrossRefGoogle Scholar
  112. Powell LW, Axelsen E, Corticosteroids in liver disease: studies on the biological conversion of prednisone to prednisolone and plasma protein binding. Gut 13: 690–696, 1972PubMedCrossRefGoogle Scholar
  113. Powell-Jackson PR, Gray BJ, Heaton RW, Costello JF, Williams R, et al. Adverse effect of rifampicin administration on steroid-dependent asthma. American Review of Respiratory Disease 128: 307–310, 1983PubMedGoogle Scholar
  114. Renner E, Horber FF, Jost G, Frey BM, Frey FJ. Effect of liver function on the metabolism of prednisone and prednisolone in humans. Gastroenterology 90: 819–828, 1986PubMedGoogle Scholar
  115. Roberts R, Wilkinson GR, Branch RA, Schenker S. Effect of age and cirrhosis on the disposition and elimination of chlordi-azepoxide. Gastroenterology 75: 479–485, 1978PubMedGoogle Scholar
  116. Rocci ML, D’Ambrosio R, Johnson NF, Jusko WJ. Prednisolone binding to albumin and transcortin in the presence of cortisol. Biochemical Pharmacology 31: 293–299, 1982aCrossRefGoogle Scholar
  117. Rocci Jr ML, Tietze KJ, Lee J, Harris H, Danzeisen J, et al. The effect of cyclosporine on the pharmacokinetics of prednisolone in renal transplant patients. Transplantation 45: 656–659, 1988PubMedCrossRefGoogle Scholar
  118. Rose IQ, Jusko WJ. Corticosteroid analysis in biological fluids by high-performance liquid chromatography. Journal of Chromatography 162: 273–280, 1979PubMedCrossRefGoogle Scholar
  119. Rose IQ, Nickelsen JA, Ellis EF, Middleton E, Jusko WJ, Prednisolone disposition in steroid-dependent asthmatic children. Journal of Allergy and Clinical Immunology 67: 188–193, 1981bPubMedCrossRefGoogle Scholar
  120. Rose IQ, Yurchak AM, Jusko WJ. Dose-dependent pharmacokinetics of prednisone and prednisolone in man. Journal of Pharmacokinetics and Biopharmaceutics 9: 389–417, 1980Google Scholar
  121. Rose IQ, Yurchak AM, Meikle AW, Jusko WJ. Effect of smoking on prednisone, prednisolone and dexamethasone pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics 9: 1–14, 1981aPubMedCrossRefGoogle Scholar
  122. Rumbaugh RC, Kramer RE, Colby HD. Dose-dependent actions of thyroxine on hepatic drug metabolism in male and female rats. Biochemical Pharmacology 27: 2027–2031, 1978PubMedCrossRefGoogle Scholar
  123. Schalm SW, Summerskill WHJ, Go VLW. Prednisone for chronic active liver disease: pharmacokinetics, including conversion to prednisolone. Gastroenterology 72: 910–913, 1977PubMedGoogle Scholar
  124. Senior DS, Shaw JT. In vitro effects of fluconazole (UK-19, 858) and ketoconazole on mouse lymphocyte proliferation and on Candida blastospors destruction by human polymorphonuclear leukocytes. International Journal of Immunopharmacology 10: 169–173, 1988PubMedCrossRefGoogle Scholar
  125. Shaffer JA, Williams SE, Turnberg LA, Houston JB, Rowland M, Absorption of prednisolone in patients with Crohn’s disease. Gut 24: 182–186, 1983PubMedCrossRefGoogle Scholar
  126. Sheiner BS, Tozer TN. Clinical pharmacokinetics: the use of plasma concentrations of drugs. In Melmon & Morelli (Eds) Clinical pharmacology, 2nd ed., pp. 71–110, Macmillan, New York, 1978Google Scholar
  127. Shukla VK, Garg SK, Mathur VS. Influence of prednisolone on antipyrine and chloramphenicol disposition in the rabbit. Pharmacology 29: 117–120, 1984PubMedCrossRefGoogle Scholar
  128. Sirgo MA, Rocci ML, Ferguson RK, Eskelman FN, Veanes PH. Effects of cimetidine and ranitidine on the conversion of prednisone to prednisolone. Clinical Pharmacology and Therapeutics 37: 534–538, 1985PubMedCrossRefGoogle Scholar
  129. Slaunwhite Jr WR, Lockie GM, Back N, Sandberg AA. Inactivity in vivo of transcortin bound cortisol. Science 135: 1062–1063, 1962PubMedCrossRefGoogle Scholar
  130. Slaunwhite Jr WR, Sandberg AA. Disposition of radioactive 17α-hydroxy-progesterone, 6α-methyl-17-acetoxy-progesterone and 6α-methylprednisolone in human subjects. Journal of Clinical Endocrinology and Metabolism 21: 753–764, 1961CrossRefGoogle Scholar
  131. Spangler AS, Antoniades HN, Sotman SL, Inderbitzin TM. Enhancement of the anti-inflammatory action of hydrocortisone by estrogens. Journal of Clinical Endocrinology and Metabolism 29: 650–655, 1969PubMedCrossRefGoogle Scholar
  132. Stuck AE, Frey BM, Frey FJ. Kinetics of prednisolone and endogenous cortisol suppression in the elderly. Clinical Pharmacology and Therapeutics 43: 354–361, 1988PubMedCrossRefGoogle Scholar
  133. Szefler SJ, Ellis EF, Brenner M, Rose JQ, Spector LS, et al. Steroid-specific and anticonvulsant interaction aspects of troleandomycin-steroid therapy. Journal of Allergy and Clinical Immunology 69: 455–460, 1982PubMedCrossRefGoogle Scholar
  134. Tanner A, Bochner F, Caffin J, Halliday J, Powell L. Dose-dependent prednisolone kinetics. Clinical Pharmacology and Therapeutics 25: 571–578, 1979PubMedGoogle Scholar
  135. Tanner AR, Halliday JW, Powell LW. Serum prednisolone levels in Crohn’s disease and coeliac disease following oral prednisolone administration. Digestion 21: 310–315, 1981PubMedCrossRefGoogle Scholar
  136. Thomas P, Richards D, Richards A, Rogers L, Evans BK, el al. Absorption of delayed-release prednisolone in ulcerative colitis and Crohn’s disease. Journal of Pharmacy and Pharmacology 37: 757–758, 1985PubMedCrossRefGoogle Scholar
  137. Tomkins GM. The enzymatic reduction of Δ4-3-ketosteroids. Journal of Biological Chemistry 225: 13–24, 1957PubMedGoogle Scholar
  138. Tsang SY, Garovoy MR, Benet LT. Immunosuppressive activity of prednisone and prednisolone and their metabolic interconversion in the mixed lymphocyte reaction. International Journal of Immunopharmacology 7: 731–737, 1985PubMedCrossRefGoogle Scholar
  139. Uribe M, Go VLW. Corticosteroid pharmacokinetics in liver disease. Clinical Pharmacokinetics 4: 233–240, 1979PubMedCrossRefGoogle Scholar
  140. Uribe M, Go VLW, Kluge D. Prednisone for chronic active hepatitis: pharmacokinetics and serum binding in patients with chronic active hepatitis and steroid major side effects. Journal of Clinical Gastroenterology 6: 331–335, 1984PubMedGoogle Scholar
  141. Uribe M, Schalm SW, Summerskill WHJ, Go VLW. Oral prednisone for chronic active liver disease: dose responses and bioavailability studies. Gut 19: 1131–1135, 1978PubMedCrossRefGoogle Scholar
  142. Vermeulen A. The metabolism of 4-14C prednisolone. Journal of Endocrinology 18: 278–291, 1959PubMedCrossRefGoogle Scholar
  143. Wassner SJ, Malekzadeh MH, Pennisi AJ, Ettenger RB, Uittenbogaart CH, et al. Allograft survival in patients receiving anticonvulsant medications. Clinical Nephrology 8: 293–297, 1977PubMedGoogle Scholar
  144. Wassner SJ, Pennisi AJ, Malekzadeh MH, Fine RN. The adverse effect of anticonvulsant therapy on renal allograft survival. Journal of Pediatrics 88: 134–137, 1976PubMedCrossRefGoogle Scholar
  145. West HJ. Prevention of peptic ulceration during corticosteroid therapy. British Medical Journal 1: 680–681, 1959CrossRefGoogle Scholar
  146. Wilkinson CF, Hetnarski K, Cantwell GP, DiCarlo FJ. Structure activity relationships in the effects of 1-alkyl-imidazoles on microsomal oxidation in vitro and in vivo. Biochemical Pharmacology 23: 2377–2386, 1974aPubMedCrossRefGoogle Scholar
  147. Wilkinson CF, Hetnarski K, Hicks LJ. Substituted imidazoles as inhibitors of microsomal oxidation and insecticide synergists. Pesticides and Biochemical Physiology 4: 9–312, 1974bGoogle Scholar
  148. Wilson CG, May CS, Paterson JW. Plasma prednisolone levels in man following administration in plain and enteric-coated forms. British Journal of Clinical Pharmacology 4: 351–355, 1977PubMedCrossRefGoogle Scholar
  149. Zumoff B, Bradlow HL, Levin J, Fukushima DK. Influence of thyroid function on the in vivo cortisol-cortisone equilibrium in man. Journal of Steroid Biochemistry 18: 437–440, 1983PubMedCrossRefGoogle Scholar
  150. Zürcher RM, Frey BM, Frey FJ. Impact of ketoconazole on the metabolism of prednisolone. Clinical Pharmacology and Therapeutics 45: 366–372, 1989aPubMedCrossRefGoogle Scholar
  151. Zürcher RM, Frey BM, Frey FJ. Ketoconazole effects on corticosteroid disposition. Clinical Pharmacology and Therapeutics, in press, 1989bGoogle Scholar

Copyright information

© Adis International Limited 1990

Authors and Affiliations

  • Brigitte M. Frey
    • 1
    • 2
  • Felix J. Frey
    • 1
    • 2
  1. 1.Medizinische PoliklinikUniversity of BerneBerneSwitzerland
  2. 2.School of MedicineUniversity of California San FranciscoCaliforniaUSA

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