Summary
The metabolic fate and ACTH-supressant activity of two injectable dexamethasone esters, 21-phosphate and 21-sulphate, were studied in healthy men. After i.v. injection of 20 mg free steroid alcohol, dexamethasone phosphate was efficiently hydrolyzed to free dexamethasone, reaching its peak plasma concentration within 5 min. About 9% of the administered dose appeared in the urine as free dexamethasone. By contrast, virtually no free dexamethasone was found in plasma and urine after injection of dexamethasone sulphate. Pharmacokinetic analysis showed that dexamethasone sulphate had a shorter plasma half-life and a higher metabolic clearance rate than free dexamethasone. A larger fraction (60%) of dexamethasone sulphate was rapidly excreted unmetabolized in urine. The plasma cortisol level was significantly suppressed for more than 24 h after dexamethasone phosphate, while the plasma cortisol profile after dexamethasone sulphate merely showed physiological circadian variations. When the steroid esters were injected after pretreatment with metyrapone, a definite suppression of plasma ACTH was noted after dexamethasone phosphate, but again, dexamethasone sulphate was ineffective. These results cast serious doubt on the clinical value of dexamethasone sulphate as an injectable glucocorticoid, and critical reevaluation of this preparation is needed.
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References
Adachi H, Nagamoto K, Hokazone H, Motomatsu K (1979) The comparison of anti-shock effect of dexamethasone disodium phosphate and dexamethasone sodium sulfate on the survival rate of mice in endotoxin shock. Anesthesia 28: 27–32 (in Japanese)
Ballard PL, Carter JP, Graham BS, Baxter JD (1975) A radioreceptor assay for evaluation of the plasma glucocorticoid activity of natural and synthetic steroids in man. J Clin Endocrinol Metab 41: 290–304
Baxter JD, Forsham RH (1972) Tissue effects of glucocorticoids. Am J Med 53: 573–589
Cavanagh D, Shingh KB (1970) Endotoxin shock in pregnancy and abortion. In: Schnur W, Nyhus LM (eds) Corticosteroids in treatment of shock. University of Illinois Press, Urbana
Duggan DE, Yeh KC, Matalia N, Ditzler CA, McMahon FG (1975) Bioavailability of oral dexamethasone. Clin Pharmacol Ther 18: 205–209
Ebata T, Osanak H, Kobayashi K, Totsuka M, Hayasaka M (1978) Effect of dexamethasone in endotoxin shock. Anesthesia 27: 355–357 (in Japanese)
Elias AN, Gwinup G (1980) Effects of some clinically encountered drugs on steroid synthesis and degradation. Metabolism 29: 582–595
Fotherby K, James F (1972) Metabolism of synthetic steroids. In: Briggs MH, Christie GA (eds) Advances in steroid biochemistry and pharmacology, vol 3. Academic Press, London New York
Greenblatt DJ, Koch-Weser J (1975) Clinical pharmacokinetics. N Engl J Med 293: 703–705
Haque N, Trasher K, Wek EE, Knowles MC, Sholiton LJ (1972) Studies on dexamethasone metabolism in man: Effect of diphenylhydantoin. J Clin Endocrinol Metab 34: 44–50
Hare LE, Yeh KC, Ditzler CA, McMahon FG, Duggan DE (1975) Bioavailability of dexamethasone. II. dexamethasone phosphate. Clin Pharmacol Ther 18: 331–337
Imai T, Sakurayama N (1978) A study of protective mechanism of glucocorticoid to shock. Folia Endocrinol Jpn 54: 87–92 (in Japanese)
Kitagawa H, Mohri T, Kitagawa M (1972) Comparative studies on anti-inflammatory effect and biological fates of 21-phosphates and -sulfates of dexamethasone and prednisolone. Arzneim Forsch 22: 402–410
Lebeau M-C, Baulieu E-E (1973) On the significance of the metabolism of steroid hormone conjugates. In: Fishman WH (ed) Metabolic conjugation and metabolic hydrolysis, vol 3. Academic Press, New York London
Lillehei RC, Dietzman RH, Mostsay GH (1972) The pharmacologic approach to the treatment of shock. Geriatrics 27: 73–94
Melby JC (1974) Systemic corticoid therapy. Pharmacology and endocrinologic considerations. Ann Intern Med 81: 505–512
Melby JC, Silber RH (1961) Clinical pharmacology of watersoluble corticosteroid esters. Am Pract 12: 156–161
Melby JC, St. Cry M (1961) Comparative studies on absorption and metabolic disposal of water-soluble corticosteroid esters. Metabolism 10: 75–82
Nakada F, Fukushima D, Bradlow HL, Hellman L, Gallagher TF (1969) Metabolism of hydrocortisone-21-sulfate in man. J Clin Endocrinol Metab 29: 1330–1334
Revesz FH, Manson AJ, Jewell JB (1970) Biological properties of estrogen sulfates. In: Bernstein S, Solomon S (eds) Chemical and biological aspects of steroid conjugation. Springer, Berlin Heidelberg New York
Robers KD, Lieberman S (1970) The biochemistry of the 3β-hydroxy-Δ5-steroid sulfates. In: Bernstein S, Solomon S (eds) Biological aspects of steroid conjugation. Springer, Berlin Heidelberg New York
Suemori I (1977) Anti-shock effects of corticosteroids observed in traumatic shoch rats. Anesthesia 26: 1124–1131 (in Japanese)
Tamm J, Voigt K (1960) Experimentelle und klinische Untersuchungen mit synthetischen wasserlöslichen Steroidkonjugaten beim Menschen. Acta Endocrinol (Suppl) 54
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Miyabo, S., Nakamura, T., Kuwazima, S. et al. A comparison of the bioavailability and potency of dexamethasone phosphate and sulphate in man. Eur J Clin Pharmacol 20, 277–282 (1981). https://doi.org/10.1007/BF00618778
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DOI: https://doi.org/10.1007/BF00618778