A cortisol suppression dose-response comparison of budesonide in controlled ileal release capsules with prednisolone.
OBJECTIVE
To assess the systemic effect of oral budesonide, given as Entocort controlled ileal release capsules, over a dose range of 3-15 mg/day, compared with that of a moderate dose (20 mg/day) of prednisolone.


METHODS
Twenty four healthy subjects were given 3, 9 or 15 mg budesonide or 20 mg prednisolone once daily, or 4.5 mg budesonide b.d., or placebo for 5 days in a randomized, double-blind crossover study. The area under the curve (AUC) of plasma cortisol concentration and the amount of cortisol excreted in the urine were monitored.


RESULTS
Both plasma and urine cortisol suppression showed a dose-response for the daily doses of budesonide. Prednisolone, 20 mg, suppressed plasma cortisol (AUC) statistically significantly more than 15 mg budesonide (P = 0.014), and 3 mg budesonide statistically significantly more than placebo (P = 0.010). No difference in AUC was detected between 9 mg and 4.5 mg budesonide b.d. Similar results for budesonide vs. placebo were obtained from urine cortisol excretion data. However, prednisolone affected urine cortisol less than it affected plasma cortisol.


CONCLUSIONS
After 5 days of administration, budesonide controlled ileal release capsules, in both clinical (9 mg/day) and high doses (15 mg/day), affected plasma cortisol less than a moderate (20 mg/day) dose of prednisolone.
Edsbäcker
S
S
Department of Clinical Pharmacology, Lund University, Lund, Sweden; Department of Astra Draco AB, Lund, Sweden. staffan.edsbacker@draco.se.astra.com
Nilsson
M
M
Larsson
P
P
D000328:Adult; D019819:Budesonide / Q000008:administration & dosage* / Q000494:pharmacology; D002214:Capsules; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007082:Ileum / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000494:pharmacology*
D002214:Capsules; D003692:Delayed-Action Preparations; D019819:Budesonide; D011241:Prednisone; D006854:Hydrocortisone