Prolonged bronchoprotection against inhaled methacholine by inhaled BI 1744, a long-acting beta(2)-agonist, in patients with mild asthma.
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.
O'Byrne
Paul M
PM
Department of Medicine, McMaster University, Hamilton, Ontario, Canada. obyrnep@mcmaster.ca
van der Linde
Just
J
Cockcroft
Donald W
DW
Gauvreau
Gail M
GM
Brannan
John D
JD
Fitzgerald
Mark
M
Watson
Richard M
RM
Milot
Joanne
J
Davis
Beth
B
O'Connor
Megan
M
Hart
Lorna
L
Korducki
Lawrence
L
Hamilton
Alan L
AL
Boulet
Louis-Philippe
LP
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
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride