Advertisement
Research Article| Volume 32, ISSUE 9, P825-833, November 01, 1992

Preliminary studies of 6β-hydroxydexamethasone and its importance in the DST

DOI:https://doi.org/10.1016/0006-3223(92)90086-F
Preliminary studies of 6β-hydroxydexamethasone and its importance in the DST
Previous ArticleDrug distribution between blood and brain as a determinant of antipsychotic drug effects
Next ArticleBupropion treatment of fluoxetine-resistant chronic fatigue syndrome
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      The role of the metabolites of dexamethasone (DEX) in the dexamethasone suppression test (DST) has never been fully elucidated. We report here our preliminary studies of 6β-hydroxydexamethasone (6 OH-Dex), a known metabolite of DEX, on the hypothalamic-pituitary-adrenal (HPA) axis of the rat; its activity in the most commonly used radioimmunoassay for plasma DEX; and its plasma concentrations in a normal human subject during the standard 1.0 mg DST.
      Six OH-Dex administered subcutaneously to rats at a dose of 1 mg/kg was able to completely suppress corticosterone production for at least 3 hr. In the IgG Corp. radioimmunoassay for plasma DEX, 6 OH-Dex was moderately cross-reactive yielding a 50% cross-reactivity of 10%. Gas chromatographic coupled mass spectroscopic analysis of human plasma samples, obtained 12 to 20 hr after the oral ingestion of 1.0 mg DEX, demonstrated similar plasma concentrations for both the parent compound and the 6-hydroxyl metabolite. The relevance of these findings, particularly to pharmacokinetic studies of the DST, is discussed.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • Arana G.W.
        • Workman R.J.
        • Baldessarini R.J.
        Association between low plasma levels of dexamethasone and elevated levels of cortisol in psychiatric patients given dexamethasone.
        Am J Psychiatry. 1984; 141: 1619-1620
        • Butler J.
        • Gray C.H.
        The metabolism of betamethasone.
        J Endocrinol. 1970; 46: 379-390
        • Carroll B.J.
        • Feinberg M.
        • Greden J.F.
        • et al.
        A specific laboratory test for the diagnosis of melancholia.
        Arch Gen Psychiatry. 1981; 38: 15-22
        • Draper R.W.
        • Berkenkopf J.
        • Carlon E.
        • Fernandez X.
        • Monahan M.
        • Lutsky B.N.
        Synthesis and topical antiinflammatory potencies of 6-keto-and Δ6-6-Acyloxybetamethasone derivatives.
        Arzneimittel Forschung. 1982; 32: 4,317-4,322
        • Dumasia M.C.
        • Horner M.W.
        • Houghton E.
        • Moss M.S.
        The urinary excretion and metabolism of dexamethasone in the horse.
        Biochem Soc Trans. 1976; 4: 119-121
        • Dumasia M.C.
        • Houghton E.
        • Moss M.S.
        • Chakraborty J.
        • Marks V.
        The biotransformation and urinary excretion of dexamethasone in equine male castrates.
        J Steroid Biochem. 1986; 25: 547-553
        • English J.E.
        • Chakraborty J.
        • Marks V.
        The metabolism of dexamethasone in the rat-effect of phenytoin.
        J Steroid Biochem. 1975; 6: 65-68
        • Girault J.
        • Istin B.
        • Fourtillan J.B.
        A rapid and highly sensitive method for the quantitative determination of dexamethasone in plasma, synovial fluid and tissues in combined gas chromatography/negative ion chemical ionization mass spectrometry.
        Biomed Environ Mass Spectrom. 1990; 19: 295-302
        • Gupta S.K.
        • Ritchie J.C.
        • Wiedemann K.
        • Holsboer F.
        Modeling the pharmacokinetics and pharmacodynamics of dexamethasone in depressed patients.
        Eur J Clin Pharmacology. 1992; 43: 51-55
        • Haque N.
        • Thrasher K.
        • Werk E.E.
        • Knowles H.C.
        • Sholiton L.J.
        Studies on dexamethasone metabolism in man: Effect of diphenylhydantoin.
        J Clin Endocrinol. 1972; 34: 44-50
        • Her G.R.
        • Watson J.T.
        Quantitative methodology for corticosteroids based on chemical oxidation to electrophilic products for electron capture-negative chemical ionization using capillary gas chromatography-mass spectrometry.
        Anal Biochem. 1985; 151: 292-298
        • Her G.R.
        • Watson J.T.
        Electron capture negative chemical ionization mass spectrometry of chemically oxidized corticosteroids.
        Biomed Environ Mass Spectrom. 1986; 13: 57-63
        • Holsboer F.
        • Haack D.
        • Gerken A.
        • Vecsei P.
        Plasma dexamethasone concentrations and different suppression response of cortisol and corticosterone in depressives and controls.
        Biol Psychiatry. 1984; 19: 281-291
        • Kalow W.
        Ethnic differences in drug metabolism.
        Clin Pharmacokinet. 1982; 7: 373-400
        • Kassem M.A.
        • Schulte K.E.
        Influence of phenylbutazone, mofebutazone and aspirin on the pharmacokinetics of dexamethasone in the rat.
        Eur J Drug Metab Pharmacokinet. 1981; 6: 11-20
        • Kayganich K.A.
        • Watson J.T.
        • Kilts C.
        • Ritchie J.
        Determination of plasma dexamethasone by chemical oxidation and electron capture negative ionization mass spectrometry.
        Biomed Environ Mass Spectrom. 1990; 19: 341-347
        • Lowry M.T.
        • Meltzer H.Y.
        Dexamethasone bioavailability: Implications for DST research.
        Biol Psychiatry. 1987; 22: 373-385
        • Lurie S.
        • Kuhn C.
        • Bartolome J.
        • Schanberg S.
        Differential sensitivity to dexamethasone suppression in an animal model of the DST.
        Biol Psychiatry. 1989; 26: 26-34
        • Minagawa K.
        • Kasuya Y.
        • Baba S.
        • Knapp G.
        • Skelly J.P.
        Identification and quantification of 6β-hydroxy-dexamethasone as a major urinary metabolite of dexamethasone in man.
        Steroids. 1986; 47: 175-188
        • Murphy B.E.P.
        Some studies of the protein-binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay.
        J Clin Endocrinol. 1967; 27: 973-990
        • Rice M.J.
        • Tredger J.M.
        • Chakraborty J.
        • Parke D.V.
        The metabolism of dexamethasone in the rat.
        Biochem Soc Trans. 1974; 2: 107-109
        • Ritchie J.C.
        • Belkin B.M.
        • Krishnan K.R.R.
        • Nemeroff C.B.
        • Carroll B.J.
        Plasma dexamethasone concentrations and the dexamethasone suppression test.
        Biol Psychiatry. 1990; 27: 159-173
        • Seutter E.
        Metabolism of systematically given corticosteroids.
        Dermatologica. 1975; 151: 129-134
        • Skrabalak D.S.
        • Maylin G.A.
        Dexamethasone metabolism in the horse.
        Steroids. 1982; 39: 233-244
        • Wiedemann K.
        • Holsboer F.
        Plasma dexamethasone kinetics during the DST after oral and intravenous administration of the test drug.
        Biol Psychiatry. 1987; 22: 1340-1348

      Article info

      Publication history

      Received in revised form: June 17, 1992
      Received: November 2, 1991

      Footnotes

      ☆This work was supported in part by National Institute of Mental Health, Grant no. MH-39393. The mass spectrometry was performed on instrumentation at Michigan State University and supported by NIH grant RR-0480-23.

      Identification

      DOI: https://doi.org/10.1016/0006-3223(92)90086-F

      Copyright

      © 1992 Published by Elsevier Inc.

      ScienceDirect

      Access this article on ScienceDirect
      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties. The content on this site is intended for healthcare professionals.


      RELX