Am. J. Respir. Crit. Care Med., Volume 156, Number 6, December 1997, 1746-1751

Effects of Budesonide and Fluticasone on 24-Hour Plasma Cortisol
A Dose-Response Study

RICHARD DONNELLY, KENNETH M. WILLIAMS, A. BARRY BAKER, CARO-ANNE BADCOCK, RICHARD O. DAY, and J. PAUL SEALE

Department of Pharmacology, University of Sydney; Department of Clinical Pharmacology, St. Vincent's Hospital, and The University of New South Wales; and Astra Pharmaceuticals, Sydney, New South Wales, Australia

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 µg/d via pMDI) and FP (750, 1,500, and 2,000 µg/d via pMDI) on integrated area under the curve of 24-h plasma cortisol profiles (AUC_24h) 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 µg) produced significant dose-dependent reductions in AUC_24h compared with placebo; e.g., percent reductions in AUC_24h 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 AUC_24h (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 AUC_24h cortisol were equivalent to the effects of three times the dose of BUD.

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