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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.
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Received in revised form: June 17, 1992
Received: November 2, 1991
☆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.
© 1992 Published by Elsevier Inc.