2. Academic Validation
  3. Pharmacological characterization of the interaction between aclidinium bromide and formoterol fumarate on human isolated bronchi

Pharmacological characterization of the interaction between aclidinium bromide and formoterol fumarate on human isolated bronchi

  • Eur J Pharmacol. 2014 Dec 15:745:135-43. doi: 10.1016/j.ejphar.2014.10.025.
Mario Cazzola 1,  Luigino Calzetta 2,  Clive P Page 3,  Paola Rogliani 1,  Francesco Facciolo 4,  Amadeu Gavaldà 5,  Maria Gabriella Matera 6
Affiliations

Affiliations

  • 1 Department of System Medicine, University of Rome 'Tor Vergata', Rome, Italy.
  • 2 Laboratory of Systems Approaches and Non Communicable Diseases, IRCCS San Raffaele Pisana, Via di Val Cannuta 247 , 00166 Rome, Italy. Electronic address: [email protected].
  • 3 Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King׳s College London, London, UK.
  • 4 Thoracic Surgery, Regina Elena National Cancer Institute, Rome, Italy.
  • 5 Almirall, Respiratory Therapeutic Area - Discovery, R&D Center Sant Feliu de Llobregat, Barcelona, Spain.
  • 6 Department of Experimental Medicine, Second University of Naples, Naples, Italy.
PMID: 25446566 DOI: 10.1016/j.ejphar.2014.10.025
Abstract

Long-acting muscarinic receptor antagonists (LAMAs) and long-acting β2-adrenoceptor agonists (LABAs) cause airway smooth muscle (ASM) relaxation via different signal transduction pathways, but there are limited data concerning the interaction between these two drug classes on human bronchi. The aim of this study was to investigate the potential synergistic interaction between aclidinium bromide and formoterol fumarate on the relaxation of human ASM. We evaluated the influence of aclidinium bromide and formoterol fumarate on the contractile response induced by acetylcholine or electrical field stimulation (EFS) on human isolated airways (segmental bronchi and bronchioles). We analyzed the potential synergistic interaction between the compounds when administered in combination by using Bliss independence (BI) theory. Both aclidinium bromide and formoterol fumarate completely relaxed segmental bronchi pre-contracted with acetylcholine (Emax: 97.5±2.6% and 96.4±1.1%; pEC50 8.5±0.1 and 8.8±0.1; respectively). Formoterol fumarate, but not aclidinium bromide, abolished the contraction induced by acetylcholine in bronchioles (Emax: 68.1±4.5% and 99.0±5.6%; pEC50 7.9±0.3 and 8.4±0.3; respectively). The BI analysis indicated synergistic interaction at low concentrations in segmental bronchi (+18.4±2.7%; P<0.05 versus expected effect) and from low to high concentrations in bronchioles (+19.7±0.9%; P<0.05 versus expected effect). Low concentrations of both drugs produced a synergistic relaxant interaction on isolated bronchi stimulated with EFS that was sustained for 6h post-treatment (+55.1±9.4%; P<0.05 versus expected effect). These results suggest that combining aclidinium bromide plus formoterol fumarate provides synergistic benefit on ASM relaxation of both medium and small human airways, which may have major implications for the use of this combination in the clinic.

Keywords

Aclidinium bromide; COPD; Formoterol fumarate; Human bronchi; LABA; LAMA; Synergistic interaction.

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