Comparative pharmacology of salmeterol and formoterol and their interaction with salbutamol in healthy volunteers

Salmeterol and formoterol display similar beta(2) selectivity to salbutamol, but both are more potent than the latter. In vitro studies suggest that salmeterol is a partial beta(2) agonist. This raises the possibility that salbutamol may not be optimally effective when administered after salmeterol. The published onset of action of salmeterol (17.6 minutes) is slower than formoterol (1.7 minutes) or salbutamol (0.8 minutes). The aim of the present study was to determine the additional effect of salbutamol when preceded by either salmeterol or formoterol. 12 healthy volunteers who responded to a histamine challenge test, participated in a placebo-controlled, single-blind crossover study. Serial dilutions of histamine were inhaled until a 20% decrease in forced expiratory volume in 1 second (FEV1) was obtained [provocation dose (PD)(20)-FEV1]. The bronchodilators were administered in a randomised way as salmeterol (50 mu g), formoterol (24 mu g), salbutamol (200 mu g) or placebo, and the combination of salmeterol, formoterol or placebo with salbutamol. The combined effect of formoterol- and salbutamol-mediated bronchodilatation differed significantly from the effect of the salmeterol and salbutamol combination (p = 0.01) at 1 minute. However, both combinations caused significant bronchodilatation at 5 minutes (p = 0.002) when compared with placebo. These results suggest that formoterol has a quicker onset of action than salmeterol and that salmeterol seemingly does not interfere with the bronchodilatory action of salbutamol.