PT  - JOURNAL ARTICLE
AU  - Jorge De Alba
AU  - Raquel Otal
AU  - Joan Antoni Fernández-Blanco
AU  - Mònica Aparici
AU  - Carlos Puig
AU  - Amadeu Gavaldà
AU  - Montserrat Miralpeix
TI  - Abediterol has higher bronchodilatory potency than other long-acting β<sub>2</sub>-receptor agonists in a guinea pig model
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P951
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P951.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P951.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - BackgroundAbediterol (LAS100977) is a novel, long-acting, inhaled β2-receptor agonist (LABA) in Phase II development for treatment of asthma and COPD.MethodsIn vivo bronchoprotective effects were assessed in anaesthetized guinea pigs in single plethysmography chambers. Compounds were nebulized and acetylcholine (ACh; 15 µg/kg iv) administered to induce bronchoconstriction. Controls received vehicle only. Percentage inhibition was calculated by referencing maximal ACh-induced increase in lung resistance to mean vehicle group response. IC50 was calculated from resistance change at 1 hour. To calculate half-life (t1/2), the inhibitory effect of submaximal doses of each LABA was measured 1, 2, 4, 6, 18, 24, 48, 72 and 96 hours post-administration.ResultsAll LABAs inhibited bronchoconstriction in a concentration-dependent manner, achieving a submaximal inhibitory effect of 89–94%. Abediterol was most potent, with a substantially lower IC50 than reference LABAs (Table). Abediterol had a substantially longer t1/2 than vilanterol, but shorter than olodaterol and indacaterol (Table). Abediterol, olodaterol and indacaterol had a sustained duration of action (DoA) with ACh-mediated bronchospasm inhibited by >50% for up to 48 hours post-administration.ConclusionAbediterol is a potent bronchodilator in guinea pigs with a DoA similar to olodaterol and indacaterol and longer than vilanterol. These results are consistent with the potent and sustained bronchodilator effects of abediterol seen in humans.View this table: