Abediterol has higher bronchodilatory potency and reduced cardiac effects versus other long-acting β 2 -agonists in dogs

Background Abediterol (LAS100977) is a novel, long-acting, inhaled β 2 -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. Methods This 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 (ID 40 ) and 10% increase in HR. Results Abediterol had a lower ID 40 (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. Conclusion In 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.