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The main objective of this study was to show dose-dependent equivalence in the systemic activity of budesonide 800 μ g day−1and 1600 μ g day−1delivered 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 cross-over 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 μ g day−1plus placebo Turbuhaler®; budesonide Easyhaler®1600 μ g day−1plus placebo Turbuhaler®; placebo Easyhaler®plus Pulmicort®Turbuhaler®800 μ g day−1; placebo Easyhaler®plus Pulmicort®Turbuhaler®1600 μ g 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 AUC0–20values (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 μ g day−1caused minimal suppression of serum cortisol AUC0-20values. Budesonide 1600 μ g day−1statistically significantly suppressed serum cortisol AUC0–20values compared with placebo. Mean morning serum cortisol values were within the reference range in all treatment groups. At a budesonide dose of 800 μ g day−1mean 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 μ g day−1dose. 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 800μ g day−1and 1600 μ g day−1inhaled from Easyhaler®had comparable systemic effects to the same doses inhaled via Turbuhaler®.
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Accepted: June 11, 2001
Received: March 6, 2001
© 2001 Harcourt Publishers Ltd. Published by Elsevier Inc.
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