A comparison of salmeterol and formoterol in attenuating airway responses to short-acting β 2-agonists

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In vitro data suggest that salmeterol, contrary to formoterol, can partly antagonise the effect of short-acting β 2-agonist rescue medication. To explore whether this occurs in vivo, we compared the effects of increasing doses (200–3200 μg) of fenoterol on the recovery of methacholine induced bronchoconstriction as well as PD 20 methacholine in 23 asthmatic patients, during two-week treatment periods with placebo, and standard doses of salmeterol or formoterol in a double blind, double-dummy, crossover study. Salmeterol showed a slightly higher propensity for the development of bronchodilator tolerance. The recovery of methacholine induced bronchoconstriction was more complete during regular use of formoterol relative to salmeterol. During regular use of both long-acting β 2-agonists the bronchoprotective efficacy of fenoterol was attenuated, but this was more pronounced during salmeterol than during formoterol. The mean maximum increase in PD 20 metacholine after the highest dose of fenoterol was 3.97 DD during placebo, 2.47 DD during formoterol ( p<0.001) and 1.81 DD during salmeterol treatment ( p<0.001). We conclude that in asthmatic patients the efficacy of short-acting β 2-adrenoceptor agonists can be significantly attenuated during regular use of long-acting β 2-agonists. In this respect, differences were observed between salmeterol and formoterol that may represent the expression of partial antagonism by salmeterol.