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Potency and duration of action of glucocorticoids

Effects of hydrocortisone, prednisone and dexamethasone on human pituitary-adrenal function
  • A.Wayne Meikle
    Correspondence
    Requests for reprints should be addressed to Dr. A. Wayne Meikle, Division of Metabolism, The University of Utah Medical Center, 50 North Medical Drive, Salt Lake City, Utah 84132.
    Footnotes
    Affiliations
    Salt Lake City, Utah, USA
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  • Frank H. Tyler
    Footnotes
    Affiliations
    Salt Lake City, Utah, USA
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  • Author Footnotes
    ∗ Clinical Investigator (5658-01) of V.A.H. Also supported in part by U.S. Public Health Service Grants RR-64 and AM-2.
    1 From the Laboratory for Study of Hereditary and Metabolic Disorders, Veterans Administration Hospital, and the Department of Internal Medicine, University of Utah College of Medicine, Salt Lake City, Utah.
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      Abstract

      This study was designed to quantitate the relative potencies of orally administered glucocorticoids and to investigate some of the factors affecting their relative potency in normal subjects. Corticosterone was measured in plasma samples obtained at 8 A.M. from eight normal adult subjects, three women and five men, following oral doses of dexamethasone, prednisone and hydrocortisone on the preceding midnight, at 6 P.M. and at 8 A.M. The half-time of disappearance of prednisolone and dexamethasone from plasma and their free concentrations in plasma were also determined. Concentrations of plasma corticosterone and cortisol showed a significant correlation (r = 0.68 to 0.99, p <0.05 to 0.001) in all subjects before and after dexamethasone therapy. The mean weighted estimates of the relative potency were calculated for each steroid as a function of time: at 8 hours, hydrocortisone 1, prednisone 3 and dexamethasone 52, and at 14 hours, hydrocortisone 1, prednisone 5.2 and dexamethasone 154. Their effects extrapolated to zero time, an estimate of their action that is independent of their rate of clearance from plasma, showed the following relative responses: hydrocortisone 1, prednisone 1.05 and dexamethasone 17. Their biologic half-times of effect were from 1.5 to 2.0 times their half-time of disappearance from plasma. A significant correlation (p <0.001) was observed between the log of the total and free concentration of unconjugated prednisolone and dexamethasone and the log of the respective doses of prednisone and dexamethasone administered at midnight. Following doses of prednisone and dexamethasone given at midnight, seven of eight subjects showed a significant correlation (p <0.05 to 0.01) between the free plasma level of prednisolone or dexamethasone and the concentration of corticosterone in the plasma sample obtained at 8 A.M. (hereinafter referred to as “8 A.M. concentration of plasma corticosterone”).
      Our data indicate that relative intrinsic biologic potency and relative rates of disappearance from plasma are two of the most important factors in determining the relative glucocorticoid potency of orally administered glucocorticoids.
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      References

        • Liddle GW
        Clinical pharmacology of the anti-inflammatory steroids.
        Clin Pharamcol Ther. 1962; 2: 615
        • Bunin JJ
        • Black RL
        • Lutwak L
        • et al.
        Studies on dexamethasone, a new synthetic steroid in rheumatoid arthritis—a preliminary report.
        Arthritis Rheum. 1958; 1: 313
        • Christy NP
        • Wallace EZ
        • Jailer JW
        Comparative effects of prednisone and cortisone in suppressing response of adrenal cortex to exogenous adrenocorticotrophin.
        J Clin Endocrinol Metab. 1956; 16: 1059
        • Frawley TF
        • Kistler H
        • Shelley T
        Effects of anti-inflammatory steroids on carbohydrate metabolism with emphasis of hypoglycemia and diabetic states.
        Ann NY Acad Sci. 1959; 82: 868
        • Nelson DH
        • Sandberg AA
        • Palmer JG
        • et al.
        Blood levels of 17-hydrocorticosteroids following the administration of adrenal steroids and their relation to levels of circulating leukocytes.
        J Clin Invest. 1952; 31: 843
        • Hodges JR
        • Vernikos J
        A comparison of the pituitary inhibitory effects of prednisone, prednisolone and hydrocortisone.
        Br J Pharmacol. 1958; 13: 98
        • Sorett LH
        Some aspects of the evolution of anti-inflammatory steroids.
        Ann NY Acad Sci. 1959; 82: 802
        • West KM
        Response of the blood glucose to glucocorticoids in man.
        Diabetes. 1959; 8: 22
        • West KM
        Relative eosinopenic and hyperglycemic potencies of glucocorticoids in man.
        Metabolism. 1958; 7: 441
        • Buus O
        • Munthe Fog CV
        • Moller PR
        The plasma hydrocortisone level during prednisolone administration as a measure of pituitary function.
        Danish Med Bull. 1962; 9: 210
        • West KM
        • Johnson PC
        • Kyriankopoulous AA
        • et al.
        The physiologic effects of dexamethasone.
        Arthritis Rheum. 1960; 3: 129
        • Black RL
        • Reefe WE
        • David JR
        • et al.
        Dexamethasone. Antirheumatic properties, hormonal effects and adverse reactions (A 16 month study).
        Arthritis Rheum. 1960; 3: 112
        • Carter ME
        • James VHT
        Comparison of effects of corticotrophin and corticosteroids on pituitary-adrenal function.
        Ann Rheum Dis. 1970; 29: 91
        • Daly JR
        • Fletcher MR
        • Glass D
        • et al.
        Comparison of effects of long-term corticotropin and corticosteroid treatment on response of plasma growth hormone, ACTH, and corticosteroid to hypoglycemia.
        Br Med J. 1974; 2: 521
        • Morris HG
        • Neuman I
        • Ellis EF
        Plasma steroid concentrations during alternate-day treatment with prednisone.
        J Allergy Clin Immunol. 1974; 54: 350
        • Boss N
        • Klug R
        • Müller OA
        • et al.
        Quantitative assay of the suppressive effect of synthetic corticoids in man.
        Acta Endocrinol. 1971; 67: 508
        • Hedner LP
        Quantitative assay of the acute hypothalamo-pituitary depressing effect of corticosteroids in man.
        J Endocrinol Metab. 1967; 37: 57
        • Shuster S
        • Williams IA
        Pituitary and adrenal functioning during administration of small doses of corticosteroids.
        Lancet. 1961; 2: 674
        • Melby JC
        Assessment of adrenocorticotropic activity with bacterial pyrogen in hypopituitary states (abstract).
        J Clin Invest. 1959; 38: 1025
        • Peterson RE
        Metabolism of adrenocorticosteroids in man.
        Ann NY Acad Sci. 1959; 82: 846
        • Meikle AW
        • Stanchfield JB
        • West CD
        • et al.
        Hydrocortisone suppression test for Cushing's syndrome. Therapy with anticonvulsants.
        Arch Intern Med. 1974; 134: 1068
        • Melby JC
        Systemic corticosteroid therapy. Pharmacology and endocrinologic considerations.
        Ann Intern Med. 1974; 81: 505
        • Sayers GL
        • Trains RH
        Adrenocorticotrophic Hormone: Adrenocortical Steroids and Their Synthetic Analogs in the Pharmacological Basis of Therapeutics.
        in: 4th ed. Macmillan Co, New York1971: 1627
        • West CD
        • Mahajan DK
        • Chavre VJ
        • et al.
        Simultaneous measurement of multiple plasma steroids by radioimmunoassay demonstrating episodic secretion.
        J Clin Endocrinol. 1973; 36: 1230
        • Meikle AW
        • Weed JA
        • Tyler FH
        Kinetics and interconversion of prednisolone and prednisone studied with new radioimmunoassay.
        J Clin Endocrinol. 1975; 41: 717
        • Meikle AW
        • Lagerquist LG
        • Tyler FH
        A plasma dexamethasone radioimmunoassay.
        Steroids. 1973; 22: 193
        • Finney DJ
        Statistical Methods in Biological Assay.
        in: 2nd ed. Hafner Publishing Co, New York1964: 103
        • Finney DJ
        Statistical Methods in Biological Assay.
        in: 2nd ed. Hafner Publishing Co, New York1964: 107
        • Finney DJ
        Statistical Methods in Biological Assay.
        in: 2nd ed. Hafner Publishing Co, New York1964: 114
        • Finney DJ
        Statistical Methods in Biological Assay.
        in: 2nd ed. Hafner Publishing Co, New York1964: 125
        • Ettinger B
        • Goldfield EB
        • Burrill KC
        • et al.
        Plasma testosterone stimulation-suppression dynamics in hirsute women. Correlation with long-term therapy.
        Am J Med. 1973; 54: 195
        • Meikle AW
        • Clarke DH
        • Tyler FH
        Cushing's syndrome resulting from a low dose of dexamethasone.
        JAMA. 1976; 235: 1592
        • Ballard PL
        • Carter JP
        • Graham BS
        • et al.
        A radioreceptor assay for evaluation of the plasma glucocorticoid activity of natural and synthetic steroids in man.
        J Clin Endocrinol Metab. 1975; 41: 290
        • DeKloet ER
        • Van Der Vies J
        • DeWied D
        The site of the suppressive action of dexamethasone on pituitary-adrenal activity.
        Endocrinology. 1974; 94: 61
        • Cantrill HL
        • Waltman SR
        • Palmberg PF
        • et al.
        In vitro determination of relative corticosteroid potency.
        J Clin Endocrinol Metab. 1975; 40: 1074
        • Kowozer M
        • Veatch L
        • Kaplan MM
        Decreased clearance of prednisolone, a factor in the development of corticosteroid side effects.
        J Clin Endocrinol Metab. 1974; 38: 407
        • Haque N
        • Thrasher K
        • Werk Jr, EE
        • et al.
        Studies on dexamethasone metabolism in man. Effect of diphenylhydantoin.
        J Clin Endocrinol Metab. 1972; 34: 44
        • Meikle AW
        • Lagerquist LG
        • Tyler FH
        Apparently normal pituitary-adrenal suppressibility in Cushing's syndrome. Dexamethasone metabolism and plasma levels.
        J Lab Clin Med. 1975; 86: 472
        • Peets EA
        • Staub M
        • Symchowicz S
        Plasma binding of betamethasone-3H, dexamethasone-3H, and cortisol-14C. A comparative study.
        Biochem Pharmacol. 1969; 18: 1655