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Systemic Effect Comparisons of Six Inhaled Corticosteroid Preparations

National Jewish Medical and Research Center, Denver, Colorado; The University of California at San Francisco, California; Penn State Medical Center, Hershey, Pennsylvania; The University of Wisconsin, Madison, Wisconsin; Thomas Jefferson University, Philadelphia, Pennsylvania; Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Harlem Hospital Center and Columbia University, New York; and McMaster University, Hamilton, Ontario, Canada

Correspondence and requests for reprints should be addressed to Richard J. Martin, M.D., National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: martinr{at}njc.org

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.

Key Words: inhaled corticosteroids • systemic effects • cortisol suppression

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