A randomized controlled assessment of the systemic activity of budesonide when given once or twice daily via Turbuhaler

Objective: To compare the effects on the hypothalamo-pituitary-adrenal (HPA ) axis of budesonide, delivered via Turbuhaler at doses of 800 mu g once da ily in the morning or evening or 400 mu g twice daily. Methods: Healthy men (n = 24) received four treatments in random order: bud esonide, 800 mu g in the morning and placebo in the evening; budesonide, 80 0 mu g in the evening and placebo in the morning; budesonide, 400 mu g in t he morning and evening; placebo in the morning and evening. Each treatment was given for 1 week, with a 2-week washout period between treatments. Bloo d samples for measurement of plasma cortisol were obtained before the eveni ng dose on day 6 of each treatment period and over the following 22 h. Results: All three budesonide regimens produced a statistically significant reduction (mean 16-19%) in the area under the curve of plasma cortisol con centration versus time over 22 h (AUC(0-22h)) compared with placebo. There were no statistically significant differences among the three regimens. The se reductions in plasma cortisol concentrations were not considered to be c linically significant. Analysis of the fractional AUCs measured 0-10 h and 10-22 h after dosing showed that evening dosing had a greater effect on noc turnal cortisol than morning dosing; daytime cortisol was reduced by all tr eatments. Conclusion: There was no significant difference between the effects on plas ma cortisol of budesonide 400 mu g twice daily and 800 mu g once daily in t he morning or evening.