A SINGLE-DOSE COMPARISON OF INHALED ALBUTEROL AND 2 FORMULATIONS OF SALMETEROL ON AIRWAY REACTIVITY IN ASTHMATIC SUBJECTS

Salmeterol is a new beta-2-selective agonist with a long duration of action. We compared the effect of 50-mu-g salmeterol administered by metered dose inhaler (MDI) and dry powder inhaler (DPI), with 200-mu-g albuterol (by MDI) on FEV1 and histamine-induced bronchoconstriction in 12 asthmatic subjects in a double-blind, placebo-controlled crossover study. Subjects were studied for 12 h on four occasions with a histamine challenge test at 1, 4, 8, and 12 h, the response being measured as the dose of histamine causing a 20% fall in FEV1 (PD20). There was no difference in the mean +/- standard error of the mean maximum increase In FEV, between salmeterol MDI, salmeterol DPI, or albuterol (0.57 +/- 0.078, 0.54 +/- 0.089, and 0.49 +/- 0.081 L, respectively); the increase following placebo was 0.25 +/- 0.082 L. The area under the 12-h time-response curve for FEV, was greater for both formulations of salmeterol (MDI and DPI) than for albuterol. The three active drugs protected against histamine-induced bronchoconstriction. The Increase in PD20 at 1 and 12 h and the area under the 12-h time-response curve for PD20 were greater following both formulations of salmeterol than after albuterol. The greater change in geometric mean PD20 values at I h after both formulations of salmeterol (2.21 and 1.88-mu-mol) relative to albuterol (0.98-mu-mol) suggests that despite similar effects on FEV1 the doses used do not have an equivalent effect on the airways. Thus 50-mu-g salmeterol, whether given by MDI or DPI, has a longer duration of action than 200-mu-g albuterol and is still effective relative to placebo 12 h after administration.