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

To compare the effects on the hypothalamo-pituitary-adrenal (HPA) axis of budesonide, delivered via Turbuhaler at doses of 800 microg once daily in the morning or evening or 400 microg twice daily.

Healthy men (n = 24) received four treatments in random order: budesonide, 800 Fg in the morning and placebo in the evening; budesonide, 800 microg in the evening and placebo in the morning; budesonide, 400 microg in the morning and evening; placebo in the morning and evening. Each treatment was given for 1 week, with a 2-week washout period between treatments. Blood samples for measurement of plasma cortisol were obtained before the evening dose on day 6 of each treatment period and over the following 22 h.

All three budesonide regimens produced a statistically significant reduction (mean 16-19%) in the area under the curve of plasma cortisol concentration versus time over 22 h (AUC0-22h) compared with placebo. There were no statistically significant differences among the three regimens. These reductions in plasma cortisol concentrations were not considered to be clinically 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 nocturnal cortisol than morning dosing; daytime cortisol was reduced by all treatments.

There was no significant difference between the effects on plasma cortisol of budesonide 400 microg twice daily and 800 microg once daily in the morning or evening.