Airway effects of salmeterol in healthy individuals

The long-acting beta(2)-agonist salmeterol has been shown in several in vitro studies to produce non-beta-mediated relaxant effects, The aim of the present study was to investigate whether these effects have any relevance in humans in vivo, Thirteen healthy individuals were studied in a randomized, double-blind, cross-over study on five separate days, The subjects were pre-treated orally with either propranolol 400 mg in order to block beta-adrenoceptor mediated effects or placebo, Two hours after drug intake, three increasing doses of salmeterol (25 + 50 + 100 mu g), salbutamol (100 + 200 + 400 mu g) or placebo were given from matched meter dose inhalers at 1-h intervals between doses, Specific airway conductance (sGAW) was measured in a body plethysmograph at the beginning of the experiment and 30 and 60 min after each inhaled dose of the beta-agonists, Salmeterol and salbutamol produced the same maximal increase in sGAW and had the same area under the dose-response curves, Pre-treatment with propranolol totally inhibited the effect of both drugs, In conclusion, salmeterol at clinically used doses did not produce any non-beta-mediated bronchodilating effect in normal individuals, measured as sGAW. Salmeterol and salbutamol showed the same efficacy but salmeterol was four times more potent than salbutamol. (C) 1995 Academic Press Limited