A randomized controlled assessment of the effects of different dosing regimens of budesonide on the HPA-axis in healthy subjects.
OBJECTIVE
To investigate the effect on the hypothalamo-pituitary-adrenal (HPA) axis of treatment with budesonide, 400 microg once daily, morning or evening, or 200 microg twice daily, and 800 microg twice daily via Turbuhaler in a randomized, placebo-controlled, double-blind, double-dummy crossover study.


METHODS
Healthy men received budesonide, 400 microg in the morning (08.00-09.00 h) or evening (20.00-21.00 h), budesonide, 200 microg twice daily, 800 microg twice daily, and placebo twice daily, for 1 week each. Plasma and urine samples were obtained over 24 h on day 7 for cortisol determination. Twenty-five subjects completed all treatments, and 27 were included in the analysis.


RESULTS
The 24 h plasma cortisol concentrations vs placebo (95% CI) were 98% (89, 108) for 400 microg in the morning, 92% (83, 100) for 400 microg in the evening, 95% (86, 104) for 200 microg twice daily, and 76% (70, 84) for 800 microg twice daily.


CONCLUSIONS
Budesonide at a dose of 400 microg day-1 via Turbuhaler had no statistically significant effect on 24 h cortisol production, irrespective of whether treatment is given once or twice daily, whereas a dose of 800 microg twice daily resulted in a statistically significant suppression vs placebo. Neither could a significant difference be found between morning and evening dosing.
Andersson
N
N
AstraZeneca R & D Lund, Sweden. Norma.Andersson@astrazeneca.com
Källén
A
A
Thorsson
L
L
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology; D019819:Budesonide / Q000008:administration & dosage* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D010919:Placebos
D001993:Bronchodilator Agents; D010919:Placebos; D019819:Budesonide; D006854:Hydrocortisone