Systemic effect comparisons of six inhaled corticosteroid preparations.


Journal Article

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.

Full Text

Cited Authors

  • Martin, RJ; Szefler, SJ; Chinchilli, VM; Kraft, M; Dolovich, M; Boushey, HA; Cherniack, RM; Craig, TJ; Drazen, JM; Fagan, JK; Fahy, JV; Fish, JE; Ford, JG; Israel, E; Kunselman, SJ; Lazarus, SC; Lemanske, RF; Peters, SP; Sorkness, CA

Published Date

  • May 2002

Published In

Volume / Issue

  • 165 / 10

Start / End Page

  • 1377 - 1383

PubMed ID

  • 12016099

Pubmed Central ID

  • 12016099

Electronic International Standard Serial Number (EISSN)

  • 1535-4970

International Standard Serial Number (ISSN)

  • 1073-449X

Digital Object Identifier (DOI)

  • 10.1164/rccm.2105013


  • eng