Salmeterol, a new inhaled beta 2-adrenergic agonist, has a longer blocking effect than albuterol on hyperventilation-induced bronchoconstriction

Abstract

The duration of the blocking effect of salmeterol (50 μg), albuterol (200 μg), and a placebo were compared in a double-blind study in 12 adult subjects with asthma who underwent hyperventilation tests with cold dry air (−20°C) on 4 study days. On the first day, the hyperventilation test was performed at various time intervals (baseline, 1,4, 6, 8, 12, and 24 hours) with spontaneous functional recovery between each test to determine the within-day within-subject variability of the response. The response was assessed by interpolating the dose of cold dry air causing a 20% fall in FEV 1. On the 3 remaining days, separated by an interval of at least 5 days, the active or placebo medication was administered after spontaneous recovery from the first hyperventilation test. Spirometry was assessed 15 minutes and 1 hour later. The hyperventilation test was then performed and repeated 4 hours after administration of the drug. The test was repeated 6, 8, 12, and 24 hours later to detect any significant blocking effect. The improvement in FEV 1 15 minutes and 1 hour after the drug was administered was 19.8% and 20.4%, as compared to baseline for albuterol, and 16.3% and 16.8% for salmeterol (not significant). The mean duration of the blocking effect was 0.25 hour for the placebo, 3.5 hours for albuterol, and 15.9 hours for salmeterol ( F = 24.5; p < 0.001; Newman-Keul's test was significant for every contrast). Eight of the 12 subjects still demonstrated some blocking effect 8 hours after taking salmeterol; this was true for only one subject receiving albuterol. We conclude that salmeterol has a significantly longer effect than albuterol on bronchoconstriction induced by hyperventilation.