title: Searching for the synergistic effect between aclidinium and formoterol: From bench to bedside.
abstract: Aim of our study was to understand if the interaction between aclidinium and formoterol administered at therapeutic doses leads to a synergistic rather than additive broncholytic effect. We tested the type of effect ex vivo on isolated human bronchi and then in vivo in COPD patients. The analysis of the interaction between aclidinium and formoterol in vitro was measured by applying the Unified Theory, whereas that in COPD patients was measured by applying the Bliss Independence criterion. Aclidinium and formoterol administered alone completely relaxed human isolated bronchial tissues sub-maximally pre-contracted with ACh in a concentration-dependent manner with similar potency (EC50: aclidinium 4.64 ± 0.78 nM, formoterol 2.71 ± 0.21), whereas the interaction of aclidinium plus formoterol produced moderate to strong synergism. Changes in FEV1 values showed that inhaled aclidinium and formoterol induced a significant and time-dependent bronchodilatory effect during the study time. The inhalation of aclidinium and formoterol in combination significantly anticipated at 5 min post-administration the bronchodilatory effect of FEV1, compared with the effect of drugs administered alone. There was a synergistic interaction for FEV1 at 5 min and from 120 min to 240 min post-inhalation, whereas from 30 min to 60 min post-administration the drug interaction was additive. This study shows that aclidinium and formoterol can produce a significant synergistic interaction that may have a role also in the clinic setting.
authors: University of Rome Tor Vergata, Department of Systems Medicine, Chair of Respiratory Medicine, Rome, Italy; University of Rome Tor Vergata, Department of Systems Medicine, Respiratory Pharmacology Research Unit, Rome, Italy; University Hospital Tor Vergata, Division of Respiratory Medicine, Rome, Italy. Electronic address: mario.cazzola@uniroma2.it.
authors: Mario
authors: M
authors: Cazzola
authors: University of Rome Tor Vergata, Department of Systems Medicine, Respiratory Pharmacology Research Unit, Rome, Italy.
authors: Luigino
authors: L
authors: Calzetta
authors: University Hospital Tor Vergata, Division of Respiratory Medicine, Rome, Italy.
authors: Josuel
authors: J
authors: Ora
authors: University of Rome Tor Vergata, Department of Systems Medicine, Chair of Respiratory Medicine, Rome, Italy; University Hospital Tor Vergata, Division of Respiratory Medicine, Rome, Italy.
authors: Ermanno
authors: E
authors: Puxeddu
authors: University of Rome Tor Vergata, Department of Systems Medicine, Chair of Respiratory Medicine, Rome, Italy; University Hospital Tor Vergata, Division of Respiratory Medicine, Rome, Italy.
authors: Paola
authors: P
authors: Rogliani
authors: Second University of Naples, Department of Experimental Medicine, Unit of Pharmacology, Naples, Italy.
authors: Maria Gabriella
authors: MG
authors: Matera
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000368:Aged; D001980:Bronchi / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D016037:Single-Blind Method; D057170:Translational Research, Biomedical; D014326:Tropanes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D014326:Tropanes; C542859:aclidinium bromide; D000068759:Formoterol Fumarate
keywords: Aclidinium; COPD; Dual bronchodilation; Formoterol; Translation research