title: Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate.
abstract: Mometasone furoate (MF) and fluticasone propionate (FP) are high potency inhaled corticosteroids. The systemic bioavailability of MF is claimed to be negligible, leading to a minimal potential for systemic adverse effects. We assessed the overnight urinary cortisol/creatinine as the primary outcome of adrenal suppression in 21 patients with persistent asthma (mean FEV1 = 91%). Patients were randomized in a crossover fashion to receive 2 weekly consecutive doubling incremental doses of either FP Accuhaler (500, 1,000, and 2,000 microg/day) or MF Twisthaler (400, 800, and 1,600 microg/day). For the 21 per protocol completed patients, there was significant suppression of overnight urinary cortisol/creatinine with high and medium doses of both drugs-as geometric mean fold suppression (95% confidence interval) from baseline: FP 2,000 microg, 1.85 (1.21-2.82, p = 0.002); FP 1,000 microg, 1.45 (1.07-1.96, p = 0.02); MF 1,600 microg, 1.92 (1.26-2.93, p = 0.001); and MF 800 microg, 1.39 (1.04-1.88, p = 0.02). For secondary outcomes of 8:00 A.M. plasma cortisol, serum osteocalcin, and early morning urinary cortisol/creatinine, there was significant suppression with MF and FP at the highest dose. Our data refute the assertion that MF has negligible systemic bioavailability and a lower potential for systemic adverse effects compared with FP.
authors.affiliation: Asthma and Allergy Research Group, Department of Medicine and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, United Kingdom.
authors.forename: Tom C
authors.initials: TC
authors.lastname: Fardon
authors.forename: Daniel K C
authors.initials: DK
authors.lastname: Lee
authors.forename: Kay
authors.initials: K
authors.lastname: Haggart
authors.forename: Lesley C
authors.initials: LC
authors.lastname: McFarlane
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D001682:Biological Availability; D016001:Confidence Intervals; D003404:Creatinine / Q000652:urine*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000068298:Fluticasone; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D008297:Male; D008875:Middle Aged; D000068656:Mometasone Furoate; D015999:Multivariate Analysis; D011244:Pregnadienediols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011336:Probability; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D016896:Treatment Outcome; D016482:Urinalysis
chemical_list: D000730:Androstadienes; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D003404:Creatinine; D000068298:Fluticasone; D006854:Hydrocortisone