Summary
The dose dependency of the pharmacokinetics of dexamethasone and its influence on the endogenous secretion of cortisol has been studied in healthy females. The maximum plasma level occurred between 1.6 and 2.0 h after doses of 0.5–3.0 mg independent of the type of administration. AUC, distribution volume, plasma clearance and cmax did not increase in proportion to the dose but only by the factor of about 0.6–0.7 after the oral administration of 0.5–1.5 mg. Comparatively high values were reached after 3.0 mg i.m. This may be due to reduced bioavailability of the oral doses. Within the first 12 h after the administration of 0.5–3.0 mg, endogenous cortisol secretion was influenced independent of dose. However, the suppressive effect after 24 h was dose dependent and amounted to approximately 24% for 0.5 mg p. o., 62% for 1.5 mg p. o. and 90% for 3.0 mg i. m. In the case of administration every second day, the integral reduction within 24 h after the administration of 0.5 mg dexamethasone was 44 to 65% and for 1.5 mg between 59 and 62%.
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References
Al-Habet S, Rogers HJ (1980) Pharmacokinetics of intravenous and oral prednisolone. Br J Clin Pharmacol 10: 503–508
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
Baxter JD, Forsham PH (1972) Tissue effects of glucocorticoids. Am J Med 53: 573
Bozler G, van Rossum (1982) Data analysis and evaluation techniques during drug development. Fischer, Stuttgart New York, p 207
Daughaday WH (1985) Binding of corticosteroids by plasma proteins. Arch Intern Med 101: 286–290
Daughaday WH, Kozak I (1958) Binding of corticosteroids by plasma proteins IV. The electrophoretic demonstration of corticosteroid binding globulin. J Clin Invest 37: 519–523
Duggan DE, Yeh KC, Matalia N, Ditzier CA, MacMahon FG (1975) Bioavailability of oral dexamethasone. Clin Pharmacol Ther 18: 205–209
Fellier H, Gleispach H, Esterbauer H (1977) Bindung von Cortisol, Fluocortolon und Difluocortolon an Humanplasmaproteine. J Clin Chem Clin Biochem 15: 545–548
Florini JR, Buyske DA (1961) Plasma protein binding of triamcinolone-H3 and Hydrocortisone-4-C14. J Biol Chem 236: 247
Haack D, Günther D, Kunkel G, Lichtwald K, Täuber U, Vecsei P (1981) Radioimmunologische Bestimmung von synthetischen Glukokortikoiden. Atemw Lungenkrh 7: 283–289
Martin IE, Tanner RJN, Clark TJH, Cochrane GM (1973) Absorption and metabolism of orally administered beclomethasone dipopionate. Clin Pharmacol Ther 15: 267–275
Miyabo S, Nakamura T, Kuwazima S, Kishida S (1981) A comparison of the bioavailability and potency of dexamethasone phosphate and sulphate in man. Eur J Clin Pharmacol 20 [4]: 277–282
Möllmann H, Brauwers H, Wagner H, Bigalke C, Rohdewald P, Straub H (1980) Vergleichende Untersuchungen über den Einfluß verschiedener triamcinolonhaltiger Kristallsuspensionen auf den Plasmacortisolspiegel. Therapiewoche 30: 1068–1084
Peets EA, Straub M, Symchowicz S (1969) Plasma binding of beta-methasone-3H, Dexamethasone-3H and cortisol-14C — a comparative study. Biochem Pharmacol 18: 1655–1663
Pickup HE, Lowe JR, Leatham PA, Rhind VM, Wright V, Downie WW (1977) Dose dependent pharmacokinetics of prednisolone. Eur J Clin Pharmacol 12: 213–219
Tanner A, Bochner F, Caffin J, Haddiday J, Powell L (1979) Dose-dependent prednisolone kinetics. Clin Pharmacol Ther 25: 571–578
Täuber U, Haack D, Nieuweboer B, Kloss G, Vecsei P, Wendt H (1984) The pharmacokinetics of fluocortolone and prednisolone after intravenous and oral administration. Clin Pharmacol Ther Toxicol 22: 48–55
Toothaker RD, Welling PG (1982) Effect of dose size on the pharmacokinetics of intravenous hydrocortisone during endogenous hydrocortisone suppression. J Pharmacokinet Biopharmaceut 10 [2]: 147–156
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Loew, D., Schuster, O. & Graul, E.H. Dose-dependent pharmacokinetics of dexamethasone. Eur J Clin Pharmacol 30, 225–230 (1986). https://doi.org/10.1007/BF00614309
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DOI: https://doi.org/10.1007/BF00614309