RT Journal Article
SR Electronic
T1 Interaction between aclidinium bromide and formoterol fumarate; effects on human bronchial smooth muscle
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P954
VO 44
IS Suppl 58
A1 Mario Cazzola
A1 Luigi Calzetta
A1 Clive P. Page
A1 Francesco Facciolo
A1 Amadeu Gavaldà
A1 Maria Gabriella Matera
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P954.abstract
AB 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.