A randomized controlled assessment of the effects of different dosing regimens of budesonide on the HPA-axis in healthy subjects

Aims To investigate the effect on the hypothalmo-pituitary-adrenal (HPA) ax is of treatment with budesonide, 400 mug once daily, morning or evening, or 200 mug twice daily, and 800 mug twice daily via Turbuhaler in a randomize d, placebo-controlled, double-blind, double-dummy crossover study. Methods Healthy men received budesonide, 400 mug in the morning (08.00-09.0 0 h) or evening (20.00-21.00 h), budesonide, 200 mug twice daily, 800 mug t wice daily, and placebo twice daily, for 1 week each. Plasma and urine samp les were obtained over 24 h on day 7 for cortisol determination. Twenty-fiv e 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 mug in the morning, 92% (83, 100) for 400 mug in the ev ening 95% (86, 104) for 200 mug twice daily, and 76% (70, 84) for 800 mug t wice daily. Conclusions Budesonide at a dose of 400 mug day(-1) via Turbuhaler had no s tatistically significant effect on 24 h cortisol production, irrespective o f whether treatment is given once or twice daily, whereas a dose of 800 mug twice daily resulted in a statistically significant suppression vs placebo . Neither could a significant difference be found between morning and eveni ng dosing.