Adrenal axis suppression unrelated to the dynamics of dosing with beclomethasone monopropionate.
OBJECTIVE
Inhaled corticosteroids (ICS) are the cornerstone of asthma treatment. At high doses they can give rise to systemic side-effects such as hypothalamic-pituitary-adrenal (HPA) axis suppression. This effect may depend on the delivery system, which in turn alters drug deposition and adsorption. We hypothesized that adrenal suppression depends on the rate of steroid absorption rather than the total steroid dose received.


METHODS
Eight healthy adult males were recruited for a randomized double-blind placebo controlled trial. Adrenocortical suppression ability was demonstrated by a 30% suppression of early morning cortisol following 1 mg dexamethasone. Subjects then attended in the evening on two occasions receiving 500 microg of intravenous beclomethasone monopropionate (17-BMP) for either 15 min or 2 h. Overnight urinary cortisol : creatinine (C : C) ratio was measured before and after the infusion and an 08.00 h serum cortisol was measured following the infusion.


RESULTS
Mean C : C pre and post 15 min infusion was 5.97 and 3.22 (P = 0.005). Mean C : C pre and post 2 h infusion was 6.31 and 4.15 (P = 0.004). Delta C : C and mean 08.00 h cortisol for 15 min and 2 h infusion was 2.74 and 2.16 and 425 nmol l(-1) and 400 nmol l(-1), respectively (P = NS).


CONCLUSIONS
The rate of infusion of 17-BMP seemed to have little effect on the degree of adrenal suppression. Individual C : C ratios were reproducible. Differences in absorption of ICS are unlikely to explain observed differences in HPA axis suppression.
Mulrennan
Siobhan A
SA
Division of Academic Medicine, University of Hull, Hull, UK.
Hogg
Joseph S
JS
Teoh
Richard C
RC
Morice
Alyn H
AH
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001507:Beclomethasone / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D001507:Beclomethasone