Lack of effect on adult and adolescent hypothalamic-pituitary-adrenal axis function with use of fluticasone furoate nasal spray.
BACKGROUND
Intranasal corticosteroids are recommended as first-line therapy for allergic rhinitis (AR), and because of their pharmacologic class, hypothalamic-pituitary-adrenal (HPA) axis function is evaluated.


OBJECTIVE
To evaluate whether cortisol production was suppressed (as a measure of HPA axis function) by 6 weeks of treatment with fluticasone furoate nasal spray, 110 microg once daily, in patients with perennial AR.


METHODS
A double-blind, randomized, placebo- and active-controlled (prednisone), parallel-group study. Outpatients aged 12 to 65 years with perennial AR for 2 years or more were from 1 center in the United States and 1 center in Canada. Pharmacodynamic and pharmacokinetic samples were collected during 24-hour domiciled visits (overnight in clinic). Measurements included change from baseline in 24-hour serum cortisol weighted mean and 24-hour urinary free cortisol excretion, total 24-hour urinary free cortisol excretion and 6-beta hydroxycortisol excretion, and plasma concentration of fluticasone furoate.


RESULTS
A total of 112 of 183 patients were randomized. Fluticasone furoate was noninferior to placebo with respect to the ratio from baseline in serum cortisol weighted mean (treatment ratio, 0.98; 95% confidence interval, 0.89 to 1.07). In contrast, use of prednisone, 10 mg once daily, significantly reduced the ratio from baseline compared with placebo. Change from baseline in 24-hour urinary cortisol excretion was similar in the fluticasone furoate and placebo groups. Plasma levels of fluticasone furoate were undetectable after 6 weeks of treatment.


CONCLUSIONS
Fluticasone furoate nasal spray, 110 microg once daily, was not associated with HPA axis suppression in patients 12 years and older with perennial AR.
Patel
Deepen
D
Allied Research International Inc, Mississauga, Ontario, Canada. DPatel@allied-research.com
Ratner
Paul
P
Clements
Diane
D
Wu
Wei
W
Faris
Melissa
M
Philpot
Edward
E
D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D018926:Anti-Allergic Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology; D012221:Rhinitis, Allergic, Perennial / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
D000730:Androstadienes; D018926:Anti-Allergic Agents; C001380:6 beta-hydroxycortisol; D011239:Prednisolone; C523187:fluticasone furoate; D006854:Hydrocortisone