Onset of action and duration of effect of formoterol and salmeterol compared to salbutamol in isolated guinea pig trachea with or without epithelium

Formoterol and salmeterol are 2 newly developed β2‐adrenoceptor agonists for inhalation with prolonged duration of effect compared with currently available β‐agonists. The clinical duration of effect has been suggested to be correlated to a decreased washability in vitro, i.e. decreased effect due to continuous washing of the organ bath. In this study we compared the washability and the onset of the relaxatory effect of formoterol (0.01 μM), salmeterol (0.05 μM) and salbutamol (0.1 μM) in isolated guinea pig trachea contracted with carbachol (0.1 μM). We also evaluated a possible influence of the epithelium on onset of action and/or duration of effect. A significant relaxatory effect of formoterol and salmeterol remained after washing, whereas of effect of salbutamol remained. We also found a rapid onset of action for both salbutamol and formoterol, but a significantly slower onset for salmeterol. Both the washability and the onset of action were found to be independent of the presence of the epithehum. Clinical aspects An increased knowledge of the mechanisms responsible for the onset of action and duration of effect of these new drugs may improve the understanding of the function of the β‐adrenoceptor in the airways. This study confirms the clinical data indicating a prolonged bronchorelaxatory effect of salmeterol and formoterol, and shows that this effect does not depend on an intact epithelium.