Comparison of the subacute effects of a new glucocorticoid, deflazacort, and prednisone on the hypothalamic-pituitary-adrenal axis of normal subjects.
The effects of deflazacort (DFL), a new oxazoline derivative of prednisolone, were compared with those of prednisone (Pd) by measuring plasma cortisol (F) levels as an index of the function of the hypothalamic-pituitary-adrenal (HPA) axis. Twelve normal volunteers received each glucocorticoid for 16 to 24 days in a double-blind cross-over trial with random allocation of subjects to treatment with DFL (24 mg/day) and Pd (20 mg/day) in clinically equivalent doses, with a washout period from 20 to 45 days between administration of the glucocorticoids. The following tests were performed in a randomized sequence: cortisol (F) circadian rhythm, insulin tolerance test (ITT), lysine-vasopressin (LVP) and B1-24 ACTH stimulation. Despite basal F suppression by DFL, the relative maximum F response (maximum F increment above basal/basal x 100) was significantly greater than control for the ITT and ACTH tests and was similar to the control after intramuscular injection of LVP, suggesting that the responses were appropriate for the basal F levels, with the HPA being reset at a lower level. After Pd, despite higher basal F levels, the F diurnal rhythm disappeared and there was no significant response to ITT, LVP or ACTH, indicating that the limiting factor in the HPA response was the reduced adrenal F production independent of the effects on the steroid-sensitive tissues of the brain including the pituitary.
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002940:Circadian Rhythm; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007328:Insulin / Q000008:administration & dosage; D008236:Lypressin / Q000097:blood; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011241:Prednisone / Q000494:pharmacology*; D011282:Pregnenediones / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D011282:Pregnenediones; D008236:Lypressin; C021988:deflazacort; D011241:Prednisone; D006854:Hydrocortisone