Comparative adrenal suppression with inhaled budesonide and fluticasone propionate in adult asthmatic patients

Background - A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis, each given by metered dose inhaler to asthmatic patients. Methods - Twelve asthmatic patients of mean age 29.9 years, with a forced expiratory volume in one second (FEV(1)) 92.9% predicted and forced expiratory flow 25-75% (FEF(25-75)) 69.5% predicted, on less than or equal to 400 mu g/day inhaled corticosteroid, were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400, 1000, 1600, 2000 mu g and fluticasone propionate 500, 1000, 1500, 2000 mu g. Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later. Results - Serum cortisol levels compared with placebo (mean 325.2 nmol/l) were suppressed by fluticasone at doses of 1500 mu g (211.6 nmol/l) and 2000 mu g (112.3 nmol/l) and by budesonide at 2000 mu g (243.4 nmol/l). Fluticasone propionate 2000 mu g produced lower absolute serum cortisol levels than budesonide 2000 mu g (95% CI for difference 42.9 to 219.2). The dose ratio (geometric mean) for the relative potency was 2.89 fold (95% CI 1.19 to 7.07). In terms of percentage suppression versus placebo, fluticasone propionate also produced greater effects (means and 95% CI for difference): budesonide 1600 mu g (16.0) versus fluticasone propionate 1500 mu g (40.9) (95% CI -0.6 to 50.6), budesonide 2000 mu g (26.0) versus fluticasone 2000 mu g (65.2) (95% CI 10.5 to 67.8). Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal Limit of the reference range (150 nmol/l) for fluticasone and five of 24 for budesonide. Fluticasone propionate also caused greater ACTH suppression than budesonide (as % versus placebo): budesonide 1600 mu g (12.0) versus fluticasone propionate 1500 mu g (31.9) (95% CI 7.6 to 32.1), budesonide 2000 mu g (13.5) versus fluticasone propionate 2000 mu g (44.4) (95% CI 13.2 to 48.7). For overnight 10 hour urinary cortisol (nmol/10 hours) there was a difference between the lowest doses of the two drugs: budesonide 400 mu g (37.2) versus fluticasone propionate 500 mu g (19.9) (95% CI 6.9 to 27.8). Conclusions - Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption. Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients.