title: Systemic effect comparisons of six inhaled corticosteroid preparations.
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.
authors.affiliation: National Jewish Medical and Research Center, Denver, Colorado 80206, USA. martinr@njc.org
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Myrna
authors.initials: M
authors.lastname: Dolovich
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.forename: Reuben M
authors.initials: RM
authors.lastname: Cherniack
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Craig
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Drazen
authors.forename: Joanne K
authors.initials: JK
authors.lastname: Fagan
authors.forename: John V
authors.initials: JV
authors.lastname: Fahy
authors.forename: James E
authors.initials: JE
authors.lastname: Fish
authors.forename: Jean G
authors.initials: JG
authors.lastname: Ford
authors.forename: Elliott
authors.initials: E
authors.lastname: Israel
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Kunselman
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Lazarus
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D001507:Beclomethasone / Q000008:administration & dosage; D019819:Budesonide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005446:Fluocinolone Acetonide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068298:Fluticasone; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D016037:Single-Blind Method; D016896:Treatment Outcome; D014221:Triamcinolone / Q000008:administration & dosage
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D005446:Fluocinolone Acetonide; D014221:Triamcinolone; D019819:Budesonide; C007734:flunisolide; D000068298:Fluticasone; D001507:Beclomethasone; D006854:Hydrocortisone