Pharmacological characterization of indacaterol, a novel once daily inhaled 2 adrenoceptor agonist, on small airways in human and rat precision-cut lung slices.
Indacaterol is a novel once daily inhaled beta(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 with 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 with 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 beta(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.
Sturton
Richard G
RG
Novartis Pharma AG, WSJ-386.12.16, P. O. Box, CH-4002 Basel, Switzerland.
Trifilieff
Alexandre
A
Nicholson
Andrew G
AG
Barnes
Peter J
PJ
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology; D000068759:Formoterol Fumarate; D006801:Humans; D066298:In Vitro Techniques; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D007189:Indans; D015363:Quinolones; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; C510790:indacaterol; D000420:Albuterol; D000068759:Formoterol Fumarate