title: Bronchoprotection with formoterol via dry powder and metered-dose inhalers in patients with asthma.
abstract: BACKGROUND
  Determination of device comparability for new inhaled medications is essential.
  
  
  OBJECTIVE
  To evaluate the methacholine bronchoprotection afforded by formoterol, 12 microg, delivered via Clickhaler and Aerolizer dry powder inhalers and a pressurized metered-dose inhaler (pMDI) in mild-to-moderate asthmatic patients.
  
  
  METHODS
  Two separate randomized, double-blind, double-dummy, crossover studies were performed. Peak bronchoprotection (30 minutes) was measured after administration of a single dose in a placebo-controlled study (n = 16). First-dose (8 hours) and trough (12 hours) protection were evaluated after 2 weeks (n = 28). Doubling dilution differences (DDD) in the methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% from baseline were compared, with equivalence defined if the 95% confidence interval was within the predefined equivalence limits of +/- 1.5 DDD (peak) and +/- 1.0 DDD (trough).
  
  
  RESULTS
  For peak single-dose effects, DDD (95% confidence interval) data showed significant protection vs placebo for all devices but no significant differences among active inhalers. For trough first-dose effects, there was significant protection vs baseline for all devices and equivalence for Clickhaler vs Aerolizer (-0.41; -0.85 to 0.04) and Aerolizer vs pMDI (-0.27; -0.66 to 0.13) but not for Clickhaler vs pMDI (-0.68; -1.12 to -0.23). For trough effects after 2 weeks, there was significant residual protection from baseline and equivalence for Clickhaler vs Aerolizer (-0.32; -0.94 to 0.30), Clickhaler vs pMDI (0.34; -0.96 to 0.27), and Aerolizer vs pMDI (-0.02; -0.57 to 0.52).
  
  
  CONCLUSIONS
  Formoterol delivered by 3 different inhalers exhibited a significant degree of peak and trough bronchoprotection after single and repeated dosing, with most comparisons being within predefined equivalence limits.
authors.affiliation: Department of Medicine and Therapeutics (Asthma and Allergy Research Group), Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland. b.j.lipworth@dundee.ac.uk
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Sims
authors.forename: Sudip K
authors.initials: SK
authors.lastname: Das
authors.forename: Alyn H
authors.initials: AH
authors.lastname: Morice
authors.forename: Brian J
authors.initials: BJ
authors.lastname: O'Connor
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000328:Adult; D000335:Aerosol Propellants; D001249:Asthma / Q000188:drug therapy*; D001985:Bronchial Provocation Tests; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D011208:Powders
chemical_list: D000318:Adrenergic beta-Agonists; D000335:Aerosol Propellants; D004983:Ethanolamines; D011208:Powders; D000068759:Formoterol Fumarate