title: Translational Study Searching for Synergy between Glycopyrronium and Indacaterol.
abstract: We aimed to explore whether the acute bronchodilation induced by indacaterol 150 μg and glycopyrronium bromide 50 μg is additive or synergistic with respect to monocomponents by testing the type of effect ex vivo on isolated human bronchi and then in vivo in COPD patients. Both indacaterol and glycopyrronium caused a concentration-dependent relaxation of human isolated bronchial tissues sub-maximally pre-contracted with acetylcholine; glycopyrronium was significantly more potent than indacaterol. The analysis of data using the Bliss Independence (BI) criterion indicated that glycopyrronium plus indacaterol produced an additive interaction at the isoeffective concentrations inducing EC20 and a significant synergistic relaxant effect at isoeffective concentrations inducing EC30. In COPD patients, the inhalation of indacaterol and glycopyrronium in combination significantly anticipated at 15 min post-administration the mean peak of bronchodilatory effect compared to the two drugs administered alone. The study of interaction between indacaterol and glycopyrronium by BI analysis evidenced an additive effect for FEV1 between 5 min and 180 min post-inhalation, with synergistic interaction at 15 min post-administration, compared to the bronchodilation induced by these drugs administered alone. This study suggests that the combination ensures a broncholytic effect that is greater than that induced by the single monocomponents.
authors.affiliation: 1Department of Systems Medicine, University of Rome Tor Vergata , Rome , Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Luigino
authors.initials: L
authors.lastname: Calzetta
authors.forename: Andrea
authors.initials: A
authors.lastname: Segreti
authors.forename: Francesco
authors.initials: F
authors.lastname: Facciolo
authors.forename: Paola
authors.initials: P
authors.lastname: Rogliani
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Matera
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; 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; D006024:Glycopyrrolate / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use; D016037:Single-Blind Method; D057170:Translational Research, Biomedical; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D007189:Indans; D015363:Quinolones; C510790:indacaterol; D006024:Glycopyrrolate
keywords: Glycopyrronium; combination therapy; indacaterol; synergy; traslational evaluation