Temporal aspects of glucocorticoid action and clinical implications

Administration of glucocorticoids is effective and necessary in various diseases, but the appearance of side effects may compromise its results. Timing as well as dosing designed to obtain, for the highest number of patients, maximal beneficial effects with minimal undesired effects, is particularly pertinent to long-term corticosteroid therapy, in view of the rhythms exhibited by the endogenous secretion of adrenal cortical and coordinating hormones, primarily ACTH. In experimental animals, properly-timed circadian treatment can be preferred to alternate-day treatment for avoiding certain side effects. To secure the desired effect each day rather than only on alternate days, a chronobiologically correct corticosteroid therapy seeks the best compromise between timing for most of the desired and least of the undesired effects. This was the aim in the design of a chronopluricorticoid drug, with the time specification on its label. The clinical use of this preparation allowed the inferential statistical demonstration of a rhythmic circadian organization maintained during therapy, while the pharmacological results gained were similar to those obtained by the conventional administration of larger doses of corticoids.