Dose equivalence and bronchoprotective effects of salmeterol and salbutamol in asthma

Abstract

Background - Salbutamol is the most widely prescribed short acting β2 agonist and salmeterol is the first long acting inhaled β2 agonist. The dose equivalence of salmeterol and salbutamol is disputed. Estimates of weight-for-weight dose ratio have ranged from 1:2 to 1:16. A study was undertaken to clarify the true dose ratio. Methods - The bronchoprotection afforded against repeated methacholine challenge by inhaled salmeterol 25μg and 100 μg and salbutamol 100 μg and 400 μg was compared in a randomised, double blind, placebo controlled, crossover trial. Subjects were 16 stable asthmatics with a baseline forced expiratory volume in one second (FEV1) of ≤65% predicted, screening concentration provoking a fall in FEV1 of 20% (PC20FEV1) of ≤ 8 mg/ml, and a shift in PC20FEV1 of more than two doubling concentration steps following inhalation of salbutamol 400 μg. On five separate occasions subjects underwent methacholine challenge before and 30 and 120 minutes after drug administration. PD20FEV1 was calculated for each challenge. FEV1 at 90 minutes after drug administration was also recorded. Results - Bronchoprotection afforded by salmeterol was increased at 120 minutes compared with 30 minutes and protection by salbutamol was decreased. Protection by both doses of salmeterol was similar to salbutamol 100 μg at 30 minutes but significantly greater at 120 minutes. FEV1 at 90 minutes was significantly greater after salmeterol 100 μg than after placebo, but there were no other significant differences between treatments. Maximal observed protection was equivalent for salmeterol 100 μg and salbutamol 400 μg. Conclusions - The data are compatible with a weight-for-weight dose ratio for salmeterol:salbutamol of ≤1:4.