Systemic Effect Comparisons of Six Inhaled Corticosteroid Preparations

• Published in: American journal of respiratory and critical care medicine Vol. 165; no. 10; pp. 1377 - 1383
• Main Authors: Martin, Richard J, Szefler, Stanley J, Chinchilli, Vernon M, Kraft, Monica, Dolovich, Myrna, Boushey, Homer A, Cherniack, Reuben M, Craig, Timothy J, Drazen, Jeffrey M, Fagan, Joanne K, Fahy, John V, Fish, James E, Ford, Jean G, Israel, Elliott, Kunselman, Susan J, Lazarus, Stephen C, Lemanske, Robert F., Jr, Peters, Stephen P, Sorkness, Christine A
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.05.2002; American Lung Association
• Subjects: Administration, Inhalation; Adrenal Cortex Hormones - administration & dosage; Adult; Aged; Androstadienes - administration & dosage; Asthma - diagnosis; Asthma - drug therapy; Beclomethasone - administration & dosage; Biological and medical sciences; 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; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Probability; Reference Values; Respiratory system; Single-Blind Method; Treatment Outcome; Triamcinolone - administration & dosage; Human; Budesonide; Corticosteroid; Flunisolide; Respiratory disease; Treatment efficiency; Antiinflammatory agent; Bioavailability; Fluticasone; Antiasthma agent; Biological activity; Asthma; Inhalation; Chemotherapy; Treatment; Obstructive pulmonary disease; Triamcinolone; Beclometasone dipropionate; Comparative study
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.2105013

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.