Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol.
The purpose of the present study was to assess the degree of protection of inhaled salmeterol against exercise-induced bronchoconstriction (EIB) after chronic compared with single dosing in patients with asthma. Twelve patients with exercise-induced asthma took part in a randomized double-blind crossover study to compare the duration of action of inhaled salmeterol 50 micrograms twice daily for 4 weeks with that of placebo. A standardized exercise test was performed at 6 h and 12 h after dosing on the first and last day of each treatment period. Salmeterol produced significant protection against EIB at 6 and 12 h after the first dose in comparison with placebo, whereas there was no significant attenuation of EIB after 4 weeks of chronic treatment with salmeterol. The percentage fall in FEV1 after exercise challenge at 6 h was (first dose): placebo 34.8 +/- 4.9% vs. salmeterol 11.9 +/- 2.8% (P < 0.05); (4 weeks): placebo 32.9 +/- 5.3% vs. salmeterol 24.0 +/- 4.4% (NS). These results suggest that tachyphylaxis may develop to the functional antagonism of salmeterol against EIB.
Ramage
L
L
Department of Respiratory Medicine, King's Cross Hospital, Dundee, U.K.
Lipworth
B J
BJ
Ingram
C G
CG
Cree
I A
IA
Dhillon
D P
DP
D000280:Administration, Inhalation; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001250:Asthma, Exercise-Induced / Q000503:physiopathology / Q000517:prevention & control*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate; D000420:Albuterol