title: Assessment of the systemic effects of beclomethasone dipropionate inhaled via Easyhaler or via Diskhaler in healthy male volunteers.
abstract: OBJECTIVE
  The objective of this study was to compare the systemic effects of a moderate dose (800 microg/day) with the highest recommended dose (1600 microg/day) of beclomethasone dipropionate (BDP) inhaled via either Easyhaler or Diskhaler in 15 healthy adult male volunteers.
  
  
  METHODS
  This was an open, placebo-controlled, randomised study conducted according to a crossover design and consisting of a 1-week baseline period and five 1-week treatment periods, each separated by a 1-week washout period. Subjects received in randomised order 800 microg/day BDP via Easyhaler, 1600 microg/day BDP via Easyhaler, placebo via Easyhaler, 800 microg/day BDP via Diskhaler and 1600 microg/day BDP via Diskhaler. Subjects inhaled BDP twice daily at 0800 hours and 2000 hours. The last dose of each period was inhaled at the study site. Venous blood samples were drawn prior to and at 2-hour intervals for 20 h after the last dose. Serum cortisol area under the curve (AUC0-20) and morning serum cortisol values were determined using radioimmunoassay. Urine for analysis of urine cortisol/creatinine ratios (UCC) was collected over a 12-h period after the last dose of each treatment period.
  
  
  RESULTS
  According to serum cortisol values, no systemic effects were detected with BDP 800 microg/day inhaled via Easyhaler. The mean (+/-SD) change in serum cortisol AUC0-20 was +118.3+/-1391 nmol h/l compared with placebo. Mean (SD) changes from placebo in serum cortisol AUC0-20 values after BDP 1600 microg/day were--546.3+/-1004 nmol h/l with Easyhaler and -769.3+/-596 nmol h/l with Diskhaler. However, there were no statistically significant differences in systemic bioactivity between the active treatments. Morning serum cortisol levels and UCC ratios were consistent with the serum cortisol AUC0-20 data.
  
  
  CONCLUSIONS
  In conclusion, BDP 800 microg/day inhaled via Easyhaler did not reduce serum cortisol AUC0-20 compared with placebo. Although the decrease in hypothalamic pituitary-adrenal (HPA) axis function after BDP 1600 microg/day was statistically significant compared with placebo, the reduction was small and similar with both devices.
authors.affiliation: Easyhaler Project, Orion Corporation, Orion Pharma, Kuopio, Finland.
authors.forename: K M
authors.initials: KM
authors.lastname: Hämäläinen
authors.forename: A
authors.initials: A
authors.lastname: Malinen
authors.forename: M
authors.initials: M
authors.lastname: Granander
authors.forename: P
authors.initials: P
authors.lastname: Toivanen
authors.forename: M
authors.initials: M
authors.lastname: Silvasti
mesh_terms: D000293:Adolescent; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D019540:Area Under Curve; D001507:Beclomethasone / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D009330:Nebulizers and Vaporizers
chemical_list: D018927:Anti-Asthmatic Agents; D001507:Beclomethasone; D006854:Hydrocortisone