title: Prolonged bronchoprotection against inhaled methacholine by inhaled BI 1744, a long-acting beta(2)-agonist, in patients with mild asthma.
abstract: BACKGROUND
  Long-acting ss(2)-agonists are an established controller medication in asthma. BI 1744 is a novel L\long-acting ss(2)-agonist with a preclinical profile that suggests 24-hour bronchodilation and bronchoprotection may be achieved.
  
  
  OBJECTIVE
  To examine the bronchoprotective effects of single doses of BI 1744 against methacholine provocation in subjects with mild asthma.
  
  
  METHODS
  Thirty-one subjects with mild asthma were randomized to receive single doses of BI 1744 (2, 5, 10, 20 microg) or placebo on separate days according to a double-blind, 5-way crossover design. Methacholine challenges were performed at 30 minutes and at 4, 8, 24, and 32 hours after each single dose of medication, and the results were expressed as PC(20) FEV(1).
  
  
  RESULTS
  All doses of BI 1744 produced statistically significant increases in the methacholine PC(20) compared with placebo as long as 32 hours. The mean (geometric SEM) methacholine PC(20) 24 hours after dosing with placebo was 1.73 (1.13) mg/mL, which increased after 2 microg to 3.86 (1.14) mg/mL, after 5 microg to 5.67 (1.14) mg/mL, after 10 microg to 9.42 (1.13) mg/mL, and after 20 microg to 13.71 (1.14) mg/mL (all P < .0001). After 32 hours, the methacholine PC(20) value remained significantly increased for all doses. No safety or tolerability concerns were identified.
  
  
  CONCLUSIONS
  BI 1744 provides significant bronchoprotection against inhaled methacholine for up to 32 hours after single-dose administration.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada. obyrnep@mcmaster.ca
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.forename: Just
authors.initials: J
authors.lastname: van der Linde
authors.forename: Donald W
authors.initials: DW
authors.lastname: Cockcroft
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
authors.forename: John D
authors.initials: JD
authors.lastname: Brannan
authors.forename: Mark
authors.initials: M
authors.lastname: Fitzgerald
authors.forename: Richard M
authors.initials: RM
authors.lastname: Watson
authors.forename: Joanne
authors.initials: J
authors.lastname: Milot
authors.forename: Beth
authors.initials: B
authors.lastname: Davis
authors.forename: Megan
authors.initials: M
authors.lastname: O'Connor
authors.forename: Lorna
authors.initials: L
authors.lastname: Hart
authors.forename: Lawrence
authors.initials: L
authors.lastname: Korducki
authors.forename: Alan L
authors.initials: AL
authors.lastname: Hamilton
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride