Effects of budesonide and fluticasone on 24-hour plasma cortisol. A dose-response study.
Comparison of the risk-benefit profiles of different inhaled glucocorticoids has been limited by inadequate information about the dose-response relationships for efficacy relative to side effects. Fluticasone propionate (FP) is twice as effective as budesonide (BUD), but the potency ratio of FP:BUD with respect to suppression of cortisol production is unknown. The effects of 5 d of treatment with BUD (800, 1,600, and 3,200 micrograms/d via pMDI) and FP (750, 1,500, and 2,000 micrograms/d via pMDI) on integrated area under the curve of 24-h plasma cortisol profiles (AUC24 h) were compared in a randomized, placebo-controlled, seven-period crossover study in normal male volunteers (n = 28). Plasma cortisol concentrations were measured during the last 24 h of each treatment period. Each treatment (except BUD 800 micrograms) produced significant dose-dependent reductions in AUC24 h compared with placebo; e.g., percent reductions in AUC24 h were 23, 41, and 69% for the three doses of BUD, and, correspondingly, 46, 85, and 93% for the three doses of FP. Model-derived measurements of dose potency ratios showed that FP was 2.9 times more potent than BUD in reducing AUC24 h (95% CI, 2.5 to 3.5) and 3.1 times more potent in reducing 8:00 A.M. plasma cortisol (95% CI, 2.4 to 4.0). Thus, on a microgram-for-microgram notional dose basis, the systemic effects of a given dose of FP on AUC24 h cortisol were equivalent to the effects of three times the dose of BUD.
Donnelly
R
R
Department of Pharmacology, University of Sydney, New South Wales, Australia.
Williams
K M
KM
Baker
A B
AB
Badcock
C A
CA
Day
R O
RO
Seale
J P
JP
D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019819:Budesonide / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D019819:Budesonide; D000068298:Fluticasone; D006854:Hydrocortisone