Potency and duration of action of glucocorticoids: Effects of hydrocortisone, prednisone and dexamethasone on human pituitary-adrenal function

Abstract

This study was designed to quantitate the relative potencies of orally administered glucocorticoids and to investigate some of the factors affecting their relative potency in normal subjects. Corticosterone was measured in plasma samples obtained at 8 A.M. from eight normal adult subjects, three women and five men, following oral doses of dexamethasone, prednisone and hydrocortisone on the preceding midnight, at 6 P.M. and at 8 A.M. The half-time of disappearance of prednisolone and dexamethasone from plasma and their free concentrations in plasma were also determined. Concentrations of plasma corticosterone and cortisol showed a significant correlation (r = 0.68 to 0.99, p <0.05 to 0.001) in all subjects before and after dexamethasone therapy. The mean weighted estimates of the relative potency were calculated for each steroid as a function of time: at 8 hours, hydrocortisone 1, prednisone 3 and dexamethasone 52, and at 14 hours, hydrocortisone 1, prednisone 5.2 and dexamethasone 154. Their effects extrapolated to zero time, an estimate of their action that is independent of their rate of clearance from plasma, showed the following relative responses: hydrocortisone 1, prednisone 1.05 and dexamethasone 17. Their biologic half-times of effect were from 1.5 to 2.0 times their half-time of disappearance from plasma. A significant correlation (p <0.001) was observed between the log of the total and free concentration of unconjugated prednisolone and dexamethasone and the log of the respective doses of prednisone and dexamethasone administered at midnight. Following doses of prednisone and dexamethasone given at midnight, seven of eight subjects showed a significant correlation (p <0.05 to 0.01) between the free plasma level of prednisolone or dexamethasone and the concentration of corticosterone in the plasma sample obtained at 8 A.M. (hereinafter referred to as “8 A.M. concentration of plasma corticosterone”). Our data indicate that relative intrinsic biologic potency and relative rates of disappearance from plasma are two of the most important factors in determining the relative glucocorticoid potency of orally administered glucocorticoids.