TY - JOUR T1 - Interaction between aclidinium bromide and formoterol fumarate; effects on human bronchial smooth muscle JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P954 AU - Mario Cazzola AU - Luigi Calzetta AU - Clive P. Page AU - Francesco Facciolo AU - Amadeu Gavaldà AU - Maria Gabriella Matera Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P954.abstract N2 - BackgroundCombining a long-acting β2-agonist (LABA) with a long-acting muscarinic antagonist (LAMA) could simplify COPD therapy.AimTo investigate the interaction of aclidinium (LAMA) and formoterol (LABA) on isolated human bronchi.MethodsBronchial rings from 18 patients were incubated in Krebs-Henseleit solution (37°C) aerated with O2/CO2 (95/5%) under 0.5–1.0 g tension. The response to aclidinium and formoterol, alone or in combination, at isoeffective concentrations, was assessed at sub-maximal tone (70% maximal contraction, EC70) induced by acetylcholine. The duration of action (20% maximal relaxation, EC20) was studied in tissue contracted with 10 Hz electrical field stimulation (EFS).Bronchial tone was expressed as % of maximal response to papaverine (Emax) and potency as the negative logarithm of IC50 or EC50 (pD2). Drug mixture effects were analyzed by Bliss Independence theory. Values (n=3) are mean±SEM.ResultsThe drugs induced potent, concentration-dependent relaxation of bronchi (pD2: aclidinium 8.5±0.1, formoterol 8.8±0.1; Emax: aclidinium 97.5±2.6%, formoterol 96.4±1.1%). Drug interaction was synergistic at low concentrations (aclidinium: 1.1–2.1 nM, formoterol 0.8–1.2 nM), enhancing relaxation +18.4±2.7%, compared with the expected effect.At low concentrations the combination enhanced the relaxant response to EFS during the first hour (p<0.001); maximal synergistic interaction was at ≅2 hours (82.36±2.54%), during washout. Relaxation (68.4±2.2%) was higher than expected (38.5±1.9%) from 0–6 hours (p<0.001).Conclusions: Aclidinium and formoterol at low concentrations synergistically inhibited smooth muscle tone. ER -