Effects of prior treatment with salmeterol and formoterol on airway and systemic beta(2) responses to fenoterol

Background - Previous studies have shown that both salmeterol and formoterol act as partial beta(2) receptor agonists in terms of antagonising the extrapulmonary responses to fenoterol in normal subjects. The aim of the present study was to extend previous observations in evaluating the effect of prior treatment with salmeterol and formoterol on bronchodilator responses to fenoterol, a full beta(2) receptor agonist, in patients with asthma. Methods - Ten stable asthmatic patients of mean (SE) age 37 (3.7) years and forced expiratory volume in one second (FEV(1)) 59.5 (4.1)% of predicted completed the study. One hour after inhaling single doses of placebo, salmeterol 25 mu g, or formoterol 12 mu g, dose-response curves to repeated doses of inhaled fenoterol were constructed (cumulative doses of 100-3200 mu g). Measurements of airway and systemic beta(2) receptor mediated responses were made at baseline, after inhalation of placebo, salmeterol, or formoterol, and after each dose of fenoterol. Results - Salmeterol and formoterol produced significant bronchodilation compared with placebo (mean difference and 95% CI compared with placebo): FEV(1), salmeterol 0.41 (95% CI 0.13 to 0.69) 1, formoterol 0.47 (95% CI 0.19 to 0.75)1. Salmeterol and formoterol had no significant effect on systemic responses compared with placebo. There were no significant differences in peak airway responses to fenoterol after treatment with salmeterol or formoterol compared with placebo (mean (pooled SE)): FEV(1), placebo 2.84(0.03)1, salmeterol 2.87(0.03)1, and formoterol 2.88 (0.03) 1. There were no significant differences in the area under the dose-response curve for any of the parameters during the dose-response curve following treatment with salmeterol or formoterol compared with placebo. There was no difference in the slope of the dose-response curves to fenoterol for FEV(1) or forced expiratory flow (FEF(25-75)) after treatment with salmeterol or formoterol compared with placebo, although there was a significant (p<0.05) attenuation of the slope in the dose-response curve for the peak expiratory flow rate (PEEP). Conclusions - Prior treatment with low doses of salmeterol or formoterol does not significantly alter bronchodilator dose-response curves to repeated doses of fenoterol in stable asthmatic patients.