Time of day of prednisolone administration in rheumatoid arthritis.

Abstract

SUMMARY Twelve patients with rheumatoid arthritis took low dosage prednisolone, mean 5 6 mg daily, at either 0800 h, 1300 h, or 2300 h in a double-blind within-patient controlled trial. Each patient was studied on each of the 3 regimens to assess control of symptoms and side effects and also to examine circadian rhythms in signs and symptoms. For several days during each drug regimen patients collected urine at each micturition and self-assessed their signs and symptoms. Circadian rhythms of finger joint swelling and of grip strength were determined, and were similar on all regimens, with morning peaks of symptoms and signs. Subjective and objective assessments showed no differences in effectiveness between the 3 times of administration of prednisolone. Urinary excretion patterns were similar to those observed in untreated people. The quantity and circadian pattern of 1 1-hydroxycorticosteroids excreted were similar to those in healthy patients, providing no evidence of adrenal cortical suppression at the dose levels studied, even when this dose was taken in the evening. A single morning dose of prednisolone appears in many patients to be as effective as a single evening dose or divided doses. It is therefore reasonable to initiate therapy with a morning-only regimen, because adrenopituitary suppression should be minimised.

Aspects of Human Chronopathology

“…Although the major symptoms of this common disease are pain, stiffness, and inflammation, systematic investigation of the temporal variation in these have been carried out only on a few occasions (Delbarre 1979;Kowanko et al 1981Kowanko et al , 1982bHarkness et al 1981Harkness et al , 1982. Circamensual and circannual studies using quantitative endpoints have never been conducted.…”

Lymphocytes are rhythmic: is this important?

“…When the glucocorticoid hormones first became reasonably easy to measure (in the early 1960s) the time of their administration was found to have a critical effect on their effect on the body, in particular in relation to interference with the adrenopituitary feedback mechanisms of endogenous production of cortisol.' Diagnostic tests using a nocturnal dose of dexamethasone were developed to investigate patients with suspected Cushing's syndrome, and are now also being used by some in the diagnosis ofpsychiatric disorders, in particular depression.2223 Experimental and clinical observations have made it quite certain that the time of administration of glucocorticoids may have an important effect on other aspects of their activity, and this may be relevant both to their effectiveness and to their toxicity.7 7a ,7 24 Single morning doses of prednisolone are still not yet standard practice, even in those circumstances where this approach is both logical and has been shown to work. In many other settings in which corticosteroids are an established method of treatment we still do not know the correct time for administration.…”

Systemic use of non‐biologic corticosteroids in orofacial diseases

“…Early morning dosing schemes are the most beneficial as they mimic the normal circadian production of hydrocortisone and reduce the risk of Cushing's phenotype (Lansang and Hustak, ). Early morning dosing not only could reduce the risk of HPA axis suppression but could also enhance the effect of prescribed agents as the effect of synthetic corticosteroids is added to the effect of naturally secreted cortisol (Kowanko et al , ). Tapering of the steroid dose should be achieved as soon as possible (Hoes et al , ).…”