title: Assessment of the systemic effects of budesonide inhaled from Easyhaler and from Turbuhaler in healthy male volunteers.
abstract: The main objective of this study was to show dose-dependent equivalence in the systemic activity of budesonide 800 microg day(-1) and 1600 microg day(-1) delivered from either Easyhaler or Turbuhaler in healthy male subjects. This single-centre study was carried out according to a randomized, double-blind, double-dummy, five-way crossover design over a 9-week period. All subjects received 1 week of treatment with the following, in randomized order, with a washout week between each treatment: budesonide Easyhaler 800 microg day(-1) plus placebo Turbuhaler; budesonide Easyhaler 1600 microg day(-1) plus placebo Turbuhaler; placebo Easyhaler plus Pulmicort Turbuhaler 800 microg day(-1); placebo Easyhaler plus Pulmicort Turbuhaler 1600 microg day(-1); placebo Easyhaler plus placebo Turbuhaler. The final inhalation of study drug was performed at the study centre, where blood and urine samples were collected. Fifteen subjects were recruited and all completed the study. Mean serum cortisol AUC0-20 values (the primary outcome variable) were comparable for each device at the two dose levels, and met the defined criteria for equivalence (90% CI 0.8-1.25 for between-treatment difference). Budesonide 800 microg day(-1) caused minimal suppression of serum cortisol AUC0-20 values, Budesonide 1600 microg day(-1) statistically significantly suppressed serum cortisol AUC0-20 values compared with placebo. Mean morning serum cortisol values were within the reference range in al treatment groups. At a budesonide dose of 800 microg day(-1) mean urine cortisol/creatinine ratio was statistically significantly higher with Easyhaler than with Turbuhaler, but there was no significant difference between the devices at the 1600 microg day(-1) dose. Serum budesonide concentrations were equivalent for each device at both dose levels. Adverse drug reactions were infrequent and mild in nature and there were no clinically significant changes in laboratory safety variables. In conclusion, in healthy male volunteers, budesonide 800 microg day(-1) and 1600 microg day inhaled from Easyhaler had comparable systemic effects to the same doses inhaled via Turbuhaler.
authors.affiliation: Orion Pharma, Kuopio, Finland. kaisa.hamalainen@orionpharma.com
authors.forename: K M
authors.initials: KM
authors.lastname: Hämäläinen
authors.forename: M
authors.initials: M
authors.lastname: Granander
authors.forename: P
authors.initials: P
authors.lastname: Toivanen
authors.forename: A
authors.initials: A
authors.lastname: Malinen
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D019819:Budesonide / Q000008:administration & dosage / Q000494:pharmacology*; D016001:Confidence Intervals; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004867:Equipment Design; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009330:Nebulizers and Vaporizers; D013810:Therapeutic Equivalency
chemical_list: D018927:Anti-Asthmatic Agents; D019819:Budesonide; D003404:Creatinine; D006854:Hydrocortisone