Effect of intranasal fluticasone propionate and triamcinolone acetonide on basal and dynamic measures of hypothalamic-pituitary-adrenal-axis activity in healthy volunteers.
BACKGROUND
Most published studies show that intranasal corticosteroids have no effect on the hypothalamic-pituitary-adrenal (HPA) axis, but there have been isolated reports to the contrary, contradicting accumulated knowledge on pharmacokinetics.


OBJECTIVE
To re-evaluate the effect of fluticasone propionate aqueous nasal spray (FPANS) and triamcinolone acetonide (TAA) aqueous nasal spray on the HPA axis using an improved study design.


METHODS
Twenty-three healthy volunteers were randomized in a double-blind, three-way crossover study. The study comprised a 4-day placebo run-in phase followed by three 4-day treatment periods (placebo, FPANS (200 microg once daily) or TAA aqueous nasal spray (220 microg once daily)), separated by 7-14 days washout intervals. Before the first, and on the last day of each treatment period, 12-h overnight urine was collected to assess cortisol excretion and cortisol creatinine ratio. Approximately 26 h after the last administration of study medication, volunteers underwent stimulation with 0.5 microg adrenocorticotropic hormone (ACTH). Serum cortisol concentrations were measured before and 20 and 30 min after injection. Blood and urine samples were analysed for cortisol by liquid chromatography tandem mass spectrometry.


RESULTS
Compared with placebo, EP or TAA had no significant effect on mean overnight (12 h) urinary cortisol excretion, and did not significantly suppress the overnight geometric mean urinary cortisol/creatinine excretion ratio. Values for serum cortisol before and after ACTH simulation showed no significant suppression, although there was a slight blunting of the HPA-axis response following TAA treatment.


CONCLUSIONS
This study confirms that there are no detectable effects on the HPA axis following short-term intranasal FP or TAA at their recommended dosages.
Bachert
C
C
University Hospital, Ghent, Belgium Institut für Atemwegsforschung GmbH, Düsseldorf, Germany. claus.bachert@rug.ac.be
Lukat
K F
KF
Lange
B
B
D000281:Administration, Intranasal; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D014222:Triamcinolone Acetonide / Q000008:administration & dosage*
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D000068298:Fluticasone; D014222:Triamcinolone Acetonide; D006854:Hydrocortisone