Systemic effect comparisons of six inhaled corticosteroid preparations

Am J Respir Crit Care Med. 2002 May 15;165(10):1377-83. doi: 10.1164/rccm.2105013.

Abstract

The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses. Systemic effect was evaluated by hourly plasma cortisol concentrations (8 P.M. to 8 A.M.), 12- and 24-hour urine cortisol concentrations, and a morning blood osteocalcin. The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect. For the six ICS and matching placebos (beclomethasone-chlorofluorocarbon [CFC], budesonide dry powder inhaler [DPI], fluticasone DPI, fluticasone-CFC metered dose inhaler [MDI], flunisolide-CFC, and triamcinolone-CFC), only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect. Thus microgram comparison of all ICS could only be performed at a 10% cortisol suppression: flunisolide-CFC - 936; triamcinolone-CFC - 787; beclomethasone-CFC - 548; fluticasone DPI - 445; budesonide DPI - 268; fluticasone-CFC MDI - 111. This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage*
  • Adult
  • Aged
  • Androstadienes / administration & dosage
  • Asthma / diagnosis
  • Asthma / drug therapy*
  • Beclomethasone / administration & dosage
  • Budesonide / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fluocinolone Acetonide / administration & dosage
  • Fluocinolone Acetonide / analogs & derivatives*
  • Fluticasone
  • Follow-Up Studies
  • Humans
  • Hydrocortisone / blood
  • Male
  • Middle Aged
  • Probability
  • Reference Values
  • Single-Blind Method
  • Treatment Outcome
  • Triamcinolone / administration & dosage

Substances

  • Adrenal Cortex Hormones
  • Androstadienes
  • Fluocinolone Acetonide
  • Triamcinolone
  • Budesonide
  • Fluticasone
  • Beclomethasone
  • flunisolide
  • Hydrocortisone