Relative potency in acute and chronic suppressive effects of prednisolone and betamethasone on the hypothalamic-pituitary-adrenal axis in man.

Abstract

The relative potency in the hypothalamic-pituitary-adrenal (HPA) suppression of both prednisolone and betamethasone was examined in an acute study with normal volunteers and in a chronic study with glucocorticoid-treated patients. Circadian rhythm of plasma cortisol was studied after a single dose administration of 5 to 30 mg prednisolone or 0.5 to 3.0 mg betamethasone at 08 : 00 hr. Morning-rise of plasma cortisol occurred on the morning after the administration of 30 mg or less prednisolone but no morning rise was noted after the administration of 1.0 mg or more betamethasone. Plasma ACTH was slightly elevated on the morning after 30 mg prednisolone administration but showed low levels throughout the night after 3.0 mg betamethasone administration.Plasma cortisol responsiveness to ACTH was examined in patients before and during therapy with either prednisolone or betamethasone.The basal cortisol level was not suppressed and the responsivenessto ACTH remained nearly normal during long-term 5 mg prednisolone therapy, but these were completely suppressed during long-term 0.5 mg betamethasone therapy.The responsiveness to ACTH was nearly normal in patients receiving alternate-day therapy with prednisolone in such large doses as 50 or 60 mg every other day, but was completely suppressed in patients receiving 1.0 mg betamethasone every other day. The relative potency of betamethasone in acute and chronic suppressive effects on the HPA system seems to be much stronger than that of prednisolone inequivalent doses with comparable anti-inflammatory effects. It is also suggested that the alternate-day therapy with such long-acting steroids as betamethasone are useless in preventing HPA suppression.

Comparison of the hypothalamic–pituitary–adrenal axis susceptibility upon single-dose i.m. depot versus long-acting i.v. triamcinolone acetonide therapy: a direct pharmacokinetic correlation

“…Our data are more consistent with the acute HPA suppressive effect of single i.v. prednisolone administration, which indeed was mild and lasted for 24 h when doses as high as 30 mg were given (Morimoto et al 1980). The rapid absorption, the shorter halflife and MRT as well as the rapid elimination observed after TAA-DHP in the present study were in agreement with the i.v.…”

“…In patients, long-term i.m. administration of TAA (for 1-5 years at 3-6-week interval) caused a complete suppression of the HPA axis and adrenal function (Mikhail et al 1969, 1973, Carson et al 1975, Morimoto et al 1980. However, these data can only be partly compared, because TAA treatment has been carried out repeatedly at a certain time interval over a year, where the cumulative systemic effect increased upon multiple dosing for markers of pharmacodynamic activity, e.g.…”

Management of acute respiratory diseases in the pediatric population: the role of oral corticosteroids

“…In many cases, these synthetic agents exert an enhanced anti-inflammatory effect and their action is more prolonged. The most widely used synthetic glucocorticoids in medical practice are listed in Table 2 [24, 27, 32]. Oral corticosteroids are classified based on their anti-inflammatory potency, which corresponds to the duration of action, and on the potency of the suppressive hypothalamic-pituitary-adrenal (HPA) axis.…”

“…Greater potency and a longer biological half-life (e.g., betamethasone and dexamethasone) may result in a stronger inhibition of the HPA axis even after the administration of a single dose. On the other hand, intermediate compounds such as prednisolone exert very little and transient suppression of the axis with no negative feedback on either the pituitary gland or hypothalamus, as shown by the absence of altered ACTH production [32]. …”