Background Abediterol (LAS100977) is a novel, long-acting, inhaled β 2 -receptor agonist (LABA) in Phase II development for treatment of asthma and COPD. Methods In 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. IC 50 was calculated from resistance change at 1 hour. To calculate half-life (t 1/2 ), the inhibitory effect of submaximal doses of each LABA was measured 1, 2, 4, 6, 18, 24, 48, 72 and 96 hours post-administration. Results All LABAs inhibited bronchoconstriction in a concentration-dependent manner, achieving a submaximal inhibitory effect of 89–94%. Abediterol was most potent, with a substantially lower IC 50 than reference LABAs (Table). Abediterol had a substantially longer t 1/2 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. Conclusion Abediterol 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. Potency IC 50 (μg/mL) Bronchoprotective half-life (hours) Abediterol 0.1 36 Indacaterol 2.0*** 51 Olodaterol 0.5*** 47 Vilanterol 1.8*** 18 ***p<0.001 vs abediterol
Alba et al. (Mon,) studied this question.