RT Journal Article SR Electronic T1 Abediterol has higher bronchodilatory potency and reduced cardiac effects versus other long-acting β2-agonists in dogs JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP P934 VO 44 IS Suppl 58 A1 Amadeu Gavaldà A1 Jose Luis Montero A1 Mònica Aparici A1 Carlos Puig A1 Christopher Doe A1 Montserrat Miralpeix YR 2014 UL http://erj.ersjournals.com/content/44/Suppl_58/P934.abstract AB BackgroundAbediterol (LAS100977) is a novel, long-acting, inhaled β2-agonist in development for COPD and asthma. We investigated the potency, duration of action (DoA) and safety index of abediterol vs olodaterol and vilanterol in beagle dogs.MethodsThis vehicle-controlled, latin-square, crossover study of anaesthetized dogs (n=4) investigated the response to acetylcholine (10 µg/kg iv) after administration of nebulized abediterol (0.03, 0.1, 0.3 and 1 µg/kg), olodaterol (0.1, 1 and 10 µg/kg) and vilanterol (3, 10 and 30 µg/kg). Airway resistance, heart rate (HR), and plasma glucose and potassium concentrations were assessed prior to and at 10, 20 and 30 minutes, and 1, 3, 6 and 24 hours post-administration. There was a ≥6 day washout between treatments. The safety index is the ratio of doses required for 40% inhibition of bronchoconstriction (ID40) and 10% increase in HR.ResultsAbediterol had a lower ID40 (0.06 µg/kg) than olodaterol (0.18 µg/kg) or vilanterol (2.87 µg/kg). Abediterol had a higher safety index (10.3) than olodaterol (4.9) and vilanterol (2.4). DoA at the highest dose of each drug devoid of HR effects was longer for abediterol (1 µg/kg, half-life 18.9±5.1 h) than olodaterol (1 µg/kg, 5.4±1.6 h) and vilanterol (10 µg/kg, 3.4±1.0 h). No changes in potassium concentration were observed. Transient changes in glucose concentration were observed at the highest dose of each compound.ConclusionIn dogs, abediterol has a more potent bronchoprotective effect with longer DoA than olodaterol and vilanterol, and reduced HR effects. These results suggest abediterol may provide sustained bronchodilation with reduced potential for cardiac effects in humans.