Tolerance to the bronchoprotective effect of salmeterol 12 hours after starting twice daily treatment

Background: Regular use of salmeterol has been associated with reduced bronchoprotective effect against methacholine as early as 24 hours after initiating treatment. Objective: To determine whether loss of the bronchoprotective effect measured one hour after salmeterol could be demonstrated 12 hours following one previous dose. Methods: Ten subjects with stable, mild asthma were enrolled in a randomized, placebo-controlled, double-blind, crossover study comparing two 2-dose treatment periods: (1) blinded salmeterol 50 mu g inhaled at bedtime, followed by unblinded salmeterol 50 mu g inhaled 12 hours later and (2) blinded placebo inhaled at bedtime, followed by unblinded salmeterol 50 mu g inhaled 12 hours later. The methacholine PC20 was measured one hour after the morning salmeterol; FEV1 was measured just prior to the morning salmeterol dose and at the start of the methacholine inhalation test. Results: The mean log methacholine PC20 recorded one hour after a single dose of salmeterol (1.20 +/- 0.17 SE) was significantly higher than the mean log methacholine PC20, recorded after two doses of salmeterol at 12-hour intervals (1.00 +/- 0.16 SE; P = .024). The mean FEV1 12 hours after salmeterol was significantly higher than the mean FEV1 recorded 12 hours after placebo (P = .0017), however, there was no significant difference between the FEV1 recordings one hour after the two unblinded doses of salmeterol. Conclusions: Tolerance to the bronchoprotective effect of salmeterol against methacholine induced bronchoconstriction occurs extremely quickly as it is evident 12 hours after starting twice daily treatment.