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

Abstract

Aims To investigate the effect on the hypothalamo-pituitary-adrenal (HPA) axis of treatment with budesonide, 400 mg once daily, morning or evening, or 200 mg twice daily, and 800 mg twice daily via Turbuhaler in a randomized, placebo-controlled, double-blind, double-dummy crossover study. Methods Healthy men received budesonide, 400 mg in the morning (08.00±09.00 h) or evening (20.00±21.00 h), budesonide, 200 mg twice daily, 800 mg 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-®ve 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 mg in the morning, 92% (83, 100) for 400 mg in the evening, 95% (86, 104) for 200 mg twice daily, and 76% (70, 84) for 800 mg twice daily. Conclusions Budesonide at a dose of 400 mg day x1 via Turbuhaler had no statistically signi®cant effect on 24 h cortisol production, irrespective of whether treatment is given once or twice daily, whereas a dose of 800 mg twice daily resulted in a statistically signi®cant suppression vs placebo. Neither could a signi®cant difference be found between morning and evening dosing