Effects of high-dose inhaled corticosteroids on plasma cortisol concentrations in healthy adults.
BACKGROUND
Recent studies suggest that inhaled corticosteroids may differ significantly in their systemic effects.


OBJECTIVE
To compare the systemic effects, as measured by plasma cortisol suppression, of inhaled beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide at doses of approximately 1000 microg twice daily.


METHODS
Sixty healthy adult male volunteers participated in this randomized, open-label, parallel-design study. Twenty-four-hour plasma cortisol determinations (cortisol-AUC24) were measured after a single dose of placebo medication and after a single dose and 7 consecutive doses of active medication.


RESULTS
After a single dose, all inhaled corticosteroid preparations caused statistically significant mean reductions in cortisol-AUC24 compared with placebo as follows: flunisolide, 7% (P= .02); budesonide, 16% (P= .001); beclomethasone, 18% (P= .003); triamcinolone, 19% (P=.001); and fluticasone, 35% (P<.001). After multiple doses, flunisolide was not significantly different from placebo (5%; P = .24), while budesonide (18%; P = .002), triamcinolone (25%; P<.001), beclomethasone (28%; P<.001), and fluticasone (79%; P<.001) all resulted in statistically significant suppression of cortisol-AUC24. After both single and multiple doses, beclomethasone, budesonide, flunisolide, and triamcinolone were not statistically different from each other, while fluticasone was significantly (P<.001) more suppressive than the other 4 medications.


CONCLUSIONS
These results indicate that there are differences in the systemic effects of inhaled corticosteroids when used in high doses and emphasize the importance of using the minimum dose of inhaled corticosteroids required to maintain control of asthma symptoms.
Brus
R
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IntroGene BV, Leiden, the Netherlands.
D000280:Administration, Inhalation; D000287:Administration, Topical; D000730:Androstadienes / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy; D001507:Beclomethasone / Q000494:pharmacology; D019819:Budesonide / Q000494:pharmacology; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives / Q000494:pharmacology; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D012016:Reference Values; D014222:Triamcinolone Acetonide / Q000494:pharmacology; D014838:Volunteers
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D005446:Fluocinolone Acetonide; D019819:Budesonide; C007734:flunisolide; D000068298:Fluticasone; D014222:Triamcinolone Acetonide; D001507:Beclomethasone; D006854:Hydrocortisone