Purpose of the Study
To characterize dose-response relationships for the effects of fluticasone propionate (FP) and budesonide (BUD) on diurnal cortisol production, and thereby obtain a quantitative estimate of the dose-potency ratio (FP:BUD) for adrenal suppression.
Twenty-eight normal male volunteers.
The effects of 5 days of treatment with BUD (800, 1600, and 3200 μg/day via pMD1[pressurized metered dose inhaler]) and FP (750, 1500, and 2000 μg/day via pMD1) on integrated area under the curve of 24-hour plasma cortisol profiles (AUC24h) were compared in a randomized, placebo-controlled, seven-period crossover study. Plasma cortisol concentrations were measured during the last 24 hours of each treatment period.
Each treatment (except BUD 800 μg) produced significant dose-dependent reductions in AUC24h compared with placebo; eg, percent reductions in AUC24h 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 (95% CI, 2.5–3.5).
On a μg-for-μg dose basis, the systemic effects of a given dose of FP on AUC24h cortisol were equivalent to the effects of three times the dose of BUD.
This is a very nice study that attempts to develop an objective assessment of the dose-response relationship of two commonly used inhaled steroids on a measure of systemic effect. The one limitation in the study is the use of a pMD1 delivery device for BUD. This method of administration is not available in the United States. The Turbuhaler device is the one approved here. At least one study shows that the systemic effect of BUD Turbuhaler is approximately twice that of a pMD1. Therefore, it appears that the systemic effects of FP pMD1 and BUD Turbuhaler are approximately the same. Similar studies are needed to characterize all of the available inhaled steroids in their respective delivery devices. In addition, a similar system is need to characterize efficacy.