Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate

Am J Respir Crit Care Med. 2004 Nov 1;170(9):960-6. doi: 10.1164/rccm.200404-500OC. Epub 2004 Jun 7.

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Glands / drug effects*
  • Adrenal Glands / metabolism
  • Adult
  • Aged
  • Androstadienes / administration & dosage
  • Androstadienes / pharmacokinetics*
  • Asthma / diagnosis
  • Asthma / drug therapy*
  • Biological Availability
  • Confidence Intervals
  • Creatinine / urine*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fluticasone
  • Follow-Up Studies
  • Humans
  • Hydrocortisone / urine*
  • Male
  • Middle Aged
  • Mometasone Furoate
  • Multivariate Analysis
  • Pregnadienediols / administration & dosage
  • Pregnadienediols / pharmacokinetics*
  • Probability
  • Respiratory Function Tests
  • Severity of Illness Index
  • Treatment Outcome
  • Urinalysis

Substances

  • Androstadienes
  • Pregnadienediols
  • Mometasone Furoate
  • Creatinine
  • Fluticasone
  • Hydrocortisone