DOSE EQUIVALENCE AND BRONCHOPROTECTIVE EFFECTS OF SALMETEROL AND SALBUTAMOL IN ASTHMA

Background - Salbutamol is the most widely prescribed short acting bet a(2) agonist and salmeterol is the first long acting inhaled beta(2) a gonist. The dose equivalence of salmeterol and salbutamol is disputed. Estimates of weight-for-weight dose ratio have ranged from 1:2 to 1:1 6. A study was undertaken to clarify the true dose ratio. Methods - Th e bronchoprotection afforded against repeated methacholine challenge b y inhaled salmeterol 25 mu g and 100 mu g and salbutamol 100 mu g and 400 mu g was compared in a randomised, double blind, placebo controlle d, crossover trial. Subjects were 16 stable asthmatics with a baseline forced expiratory volume in one second (FEV1) of greater than or equa l to 65% predicted, screening concentration provoking a fall in FEV1 o f 20% (PC20FEV1) of less than or equal to 8 mg/ml, and a shift in PC20 FEV1 of more than two doubling concentration steps following inhalatio n of salbutamol 400 mu g. On five separate occasions subjects underwen t methacholine challenge before and 30 and 120 minutes after drug admi nistration. PD20FEV1 was calculated for each challenge. FEV1 at 90 min utes after drug administration was also recorded. Results - Bronchopro tection afforded by salmeterol was increased at 120 minutes compared w ith 30 minutes and protection by salbutamol was decreased. Protection by both doses of salmeterol was similar to salbutamol 100 mu g at 30 m inutes but significantly greater at 120 minutes. FEV1 at 90 minutes wa s significantly greater after salmeterol 100 mu g than after placebo, but there were no other significant differences between treatments. Ma ximal observed protection was equivalent for salmeterol 100 mu g and s albutamol 400 mu g. Conclusions - The data are compatible with a weigh t-for-weight dose ratio for salmeterol:salbutamol of less than or equa l to 1:4.