Rapid Onset of Tolerance to the Bronchoprotective Effect of Salmeterol

摘要: Introduction Twice-daily inhaled salmeterol for 4 weeks produces marked reducton in its acute bronchoprotective effect against methacholine. This investigation examined the onset of this over 5 days, and also assessed cross-tolerance with salbutamol. Subjects methods Ten asthmatic volunteers who were able to withhold s 2 -agonist therapy before during study participated a double-blind, crossover, placebo-controlled two random-order treatment periods: salmeterol, 50 pg twice day seven doses, placebo similar fashion. Methacholine inhalation tests done 1 h after doses 1, 3, 5, 7, then 24 last dose inhaler 10 minutes 200 Results Baseline FEV value 7 ( ie , 12 salmeterol) was significantly higher than all other (n=7) values. Twenty-four hours no different from that period. The geometric mean methacholine concentration causing 20% fall (PC 20 ) first (6.1 mg/mL) statistically achieved min salbutamol period (8.3 mg/mL), these (analysis variance, p Conclusions Tolerance significant progressively increased seventh dose. regular use doses.