The long-acting β2-agonist (LABA) / long-acting muscarinic antagonist (LAMA) fixed dose combination (FDC) therapy represents the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD). Nevertheless, conflicting clinical findings still exist on the real benefit of the LABA/LAMA FDCs. Therefore, we investigated whether combining the LABA vilanterol with the LAMA umeclidinium may induce synergistic bronchorelaxant effect in isolated airways. The effect of umeclidinium and vilanterol, administered alone, in combination at the ratio of concentrations reproducing the doses delivered by Anoro(®) Ellipta(®) (55:22), or at isoeffective low concentrations, was investigated on the cholinergic contractile tone induced by the parasympathetic activation of human isolated airways. The interaction was analyzed by using the Bliss Independence and Unified Theory models. Umeclidinium and vilanterol induced a concentration-dependent relaxation of isolated bronchi, with umeclidinium significantly (P < 0.05) more potent than vilanterol (Emax at 10Hz: umeclidium 102.6 ± 6.8%, vilanterol 75.1 ± 13.8%; pEC50 at 10Hz: umeclidinium 8.6 ± 0.4, vilanterol 6.9 ± 0.6). When administered at 55:22 concentration-ratio, umeclidinium plus vilanterol completely relaxed the isolated airways (Emax at 10Hz: 99.6 ± 8.0%; pEC50 at 10Hz: 8.2 ± 0.4). No synergistic interaction was detected for umeclidinium/vilanterol combined at 55:22 ratio, whereas strong synergism was elicited when the drugs were administered at low isoeffective concentrations (+ 41.4 ± 5.8% vs. monocomponents), leading to submaximal relaxant effect (81.4 ± 5.8%). Umeclidinium and vilanterol are imbalanced when combined at 55:22 ratio, with umeclidinium over-dosed, or vice versa vilanterol under-dosed. Specific studies are needed to identify the dose ratio of umeclidinium/vilanterol combination to guarantee equipotency concentrations of each component into the lung, and induce synergistic bronchodilation.
Calzetta, L., Rogliani, P., Facciolo, F., Rendina, E., Cazzola, M., Matera, M. (2017). Pharmacological characterization of the interaction between umeclidinium and vilanterol in human bronchi. EUROPEAN JOURNAL OF PHARMACOLOGY [10.1016/j.ejphar.2017.07.026].
Pharmacological characterization of the interaction between umeclidinium and vilanterol in human bronchi
CALZETTA , LUIGINO;ROGLIANI, PAOLA;CAZZOLA, MARIO;
2017-01-01
Abstract
The long-acting β2-agonist (LABA) / long-acting muscarinic antagonist (LAMA) fixed dose combination (FDC) therapy represents the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD). Nevertheless, conflicting clinical findings still exist on the real benefit of the LABA/LAMA FDCs. Therefore, we investigated whether combining the LABA vilanterol with the LAMA umeclidinium may induce synergistic bronchorelaxant effect in isolated airways. The effect of umeclidinium and vilanterol, administered alone, in combination at the ratio of concentrations reproducing the doses delivered by Anoro(®) Ellipta(®) (55:22), or at isoeffective low concentrations, was investigated on the cholinergic contractile tone induced by the parasympathetic activation of human isolated airways. The interaction was analyzed by using the Bliss Independence and Unified Theory models. Umeclidinium and vilanterol induced a concentration-dependent relaxation of isolated bronchi, with umeclidinium significantly (P < 0.05) more potent than vilanterol (Emax at 10Hz: umeclidium 102.6 ± 6.8%, vilanterol 75.1 ± 13.8%; pEC50 at 10Hz: umeclidinium 8.6 ± 0.4, vilanterol 6.9 ± 0.6). When administered at 55:22 concentration-ratio, umeclidinium plus vilanterol completely relaxed the isolated airways (Emax at 10Hz: 99.6 ± 8.0%; pEC50 at 10Hz: 8.2 ± 0.4). No synergistic interaction was detected for umeclidinium/vilanterol combined at 55:22 ratio, whereas strong synergism was elicited when the drugs were administered at low isoeffective concentrations (+ 41.4 ± 5.8% vs. monocomponents), leading to submaximal relaxant effect (81.4 ± 5.8%). Umeclidinium and vilanterol are imbalanced when combined at 55:22 ratio, with umeclidinium over-dosed, or vice versa vilanterol under-dosed. Specific studies are needed to identify the dose ratio of umeclidinium/vilanterol combination to guarantee equipotency concentrations of each component into the lung, and induce synergistic bronchodilation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
