Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate.
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.
Fardon
Tom C
TC
Asthma and Allergy Research Group, Department of Medicine and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, United Kingdom.
Lee
Daniel K C
DK
Haggart
Kay
K
McFarlane
Lesley C
LC
Lipworth
Brian J
BJ
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
D000730:Androstadienes; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D003404:Creatinine; D000068298:Fluticasone; D006854:Hydrocortisone