Received for publication July 30, 2007.
Revised October 3, 2007.
Accepted for publication October 3, 2007.

Pharmacological characterisation of indacaterol, a novel once-daily inhaled ₂-adrenoceptor agonist, on small airways in human and rat precision-cut lung slices

Abstract

Indacaterol is a novel once-daily inhaled ₂ adrenoceptor agonist in clinical development. This study compared the properties of indacaterol with salmeterol, formoterol and albuterol on small airways in precision-cut lung slices from human and rat contracted with carbachol and serotonin, respectively. In human lung slices, the rank order of potency was formoterol salmeterol > indacaterol > albuterol, respectively. Indacaterol had similar intrinsic efficacy to formoterol, followed by albuterol and salmeterol. The onset of action was fast for albuterol, formoterol and indacaterol whereas it was significantly slower for salmeterol. The duration of action ranking was indacaterol > salmeterol > formoterol > albuterol. When compared to human lung slices, in the rat lung slices, similar potency, intrinsic efficacy and onset of action were observed for indacaterol, formoterol and salmeterol. Albuterol had an increased potency when compared to human lung slices and a slower onset of action. In conclusion, our results show that the human lung slice system seems to be a good model to study the clinical properties of inhaled long acting ₂ adrenoceptor agonists and that caution is needed extrapolating from rat model to humans. Finally, using the human lung slice model, we have characterized indacaterol as a fast acting compound with a longer duration of action than salmeterol and formoterol.

Key words: COPD, asthma, beta-2 adrenergic agonist, human lung slices, rat lung slices, relaxation