Systemic effect comparisons of six inhaled corticosteroid preparations.
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.
Martin
Richard J
RJ
National Jewish Medical and Research Center, Denver, Colorado 80206, USA. martinr@njc.org
Szefler
Stanley J
SJ
Chinchilli
Vernon M
VM
Kraft
Monica
M
Dolovich
Myrna
M
Boushey
Homer A
HA
Cherniack
Reuben M
RM
Craig
Timothy J
TJ
Drazen
Jeffrey M
JM
Fagan
Joanne K
JK
Fahy
John V
JV
Fish
James E
JE
Ford
Jean G
JG
Israel
Elliott
E
Kunselman
Susan J
SJ
Lazarus
Stephen C
SC
Lemanske
Robert F
RF
Peters
Stephen P
SP
Sorkness
Christine A
CA
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
D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D005446:Fluocinolone Acetonide; D014221:Triamcinolone; D019819:Budesonide; C007734:flunisolide; D000068298:Fluticasone; D001507:Beclomethasone; D006854:Hydrocortisone