Emerging trends in the therapy of COPD: bronchodilators as mono- and combination therapies

Fitzgerald, Mary; Fox, Jonathan

doi:10.1016/j.drudis.2007.04.003

Cited by 33 publications

(21 citation statements)

References 46 publications

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“…Because of the central role of bronchodilators in the treatment of both diseases, there is an interest in developing once-daily LABAs as an attempt to improve patient compliance and disease control (Cazzola et al, 2010). Indeed, the development of new inhaled corticosteroids, which can be used as a once-daily regimen, has provided additional rationale for the development of new ultra-LABAs that can be used in once-a-day combinations (Fitzgerald and Fox, 2007).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Characterization of Abediterol, a Novel Inhaled β₂-Adrenoceptor Agonist with Long Duration of Action and a Favorable Safety Profile in Preclinical Models

Aparici¹,

Gómez‐Angelats²,

Vilella³

et al. 2012

J Pharmacol Exp Ther

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Abediterol is a novel potent, long-acting inhaled ␤ 2 -adrenoceptor agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. Abediterol shows subnanomolar affinity for the human ␤ 2 -adrenoceptor and a functional selectivity over ␤ 1 -adrenoceptors higher than that of formoterol and indacaterol in both a cellular model with overexpressed human receptors and isolated guinea pig tissue. Abediterol is a full agonist at the human ␤ 2 -adrenoceptor (E max ϭ 91 Ϯ 5% of the maximal effect of isoprenaline). The potency and onset of action that abediterol shows in isolated human bronchi (EC 50 ϭ 1.9 Ϯ 0.4 nM; t 1 ⁄2 onset ϭ 7-10 min) is not significantly different from that of formoterol, but its duration of action (t 1 ⁄2 ϳ 690 min) is similar to that of indacaterol. Nebulized abediterol inhibits acetylcholine-induced bronchoconstriction in guinea pigs in a concentration-dependent manner, with higher potency and longer duration of action (t 1 ⁄2 ϭ 36 h) than salmeterol (t 1 ⁄2 ϭ 6 h) and formoterol (t 1 ⁄2 ϭ 4 h) and similar duration of action to indacaterol up to 48 h. In dogs, the bronchoprotective effect of abediterol is more sustained than that of salmeterol and indacaterol at doses without effects on heart rate, thus showing a greater safety margin (defined as the ratio of dose increasing heart rate by 5% and dose inhibiting bronchospasm by 50%) than salmeterol, formoterol, and indacaterol (5.6 versus 3.3, 2.2, and 0.3, respectively). In conclusion, our results suggest that abediterol has a preclinical profile for once-daily dosing in humans together with a fast onset of action and a favorable cardiovascular safety profile.

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Section: Introductionmentioning

confidence: 99%

Pharmacological Characterization of Abediterol, a Novel Inhaled β₂-Adrenoceptor Agonist with Long Duration of Action and a Favorable Safety Profile in Preclinical Models

Aparici¹,

Gómez‐Angelats²,

Vilella³

et al. 2012

J Pharmacol Exp Ther

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“…A combination of indacaterol, glycopyrronium bromide and mometasone seems to be a real possibility [97]. A combination of milveterol or GSK-642444 with darotropium bromide and fluticasone furoate is another valid option, whereas the combination of LAS-40369, an association of aclidinium plus an undisclosed ICS under development, with formoterol is a potential possibility that should be explored.…”

Section: Laba Lama and Ics Or Novel Anti-inflammatory Compoundsmentioning

confidence: 99%

“…Combinations containing formoterol and the once-daily ICS mometasone (MFF258) or formoterol and ciclesonide in a single inhalation device are undergoing development [97]. A next-generation once-daily combination consisting of fluticasone furoate, a new long-acting ICS, and milveterol, was stated to be in phase II studies in asthma and COPD.…”

Section: Laba and Ics Undergoing Developmentmentioning

confidence: 99%

“…Several companies are also adopting a different approach and have a dimer molecule in which a bifunctional mechanism of action, combining both muscarinic antagonist and b 2 -agonist pharmacology, is present in a single molecule, which is known as a dual-acting muscarinic antagonist-b 2 -agonist (MABA) bronchodilator [97]. MABAs have the advantage of delivering a fixed ratio into every region of the lung, reducing the complexity of combination inhalers.…”

Section: Novel Combinationsmentioning

confidence: 99%

“…The development of once-daily dual-action ultra-LABA/ LAMA combination products may also serve as a basis for improved triple therapy combinations through co-formulation with novel ICSs or novel anti-inflammatory compounds, such as inhaled phosphodiesterase (PDE) 4 inhibitors, that could deliver three complementary therapeutic effects in patients with asthma and, mainly, COPD [7,88,97]. The potential for these therapeutic strategies to be administered once daily simplifies patient treatment regimens and therefore increases the likelihood of compliance with therapy.…”

Section: Laba Lama and Ics Or Novel Anti-inflammatory Compoundsmentioning

confidence: 99%

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Emerging inhaled bronchodilators: an update

Cazzola¹,

Matera²

2009

Eur Respir J

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Bronchodilators remain central to the symptomatic management of chronic obstructive pulmonary disease and asthma, and, for this reason and also because the patent protection of many bronchodilators has expired, several companies have reinitiated research into the field.The only limits set for the development of a long-lasting bronchodilator with a new product profile are medical needs and marketing opportunities. The incorporation of once-daily dose administration is an important strategy for improving adherence and is a regimen preferred by most patients.A variety of b 2 -agonists and antimuscarinic agents with longer half-lives and inhalers containing a combination of several classes of long-acting bronchodilator are currently under development.The present article reviews all of the most important compounds under development, describing what has been done and discussing their genuine advantage.

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β‐Adrenoceptor Agonists and Asthma

Gaviraghi

2010

Analogue‐Based Drug Discovery II

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Emerging trends in the therapy of COPD: bronchodilators as mono- and combination therapies

Cited by 33 publications

References 46 publications

Pharmacological Characterization of Abediterol, a Novel Inhaled β₂-Adrenoceptor Agonist with Long Duration of Action and a Favorable Safety Profile in Preclinical Models

Pharmacological Characterization of Abediterol, a Novel Inhaled β₂-Adrenoceptor Agonist with Long Duration of Action and a Favorable Safety Profile in Preclinical Models

Emerging inhaled bronchodilators: an update

β‐Adrenoceptor Agonists and Asthma

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Emerging trends in the therapy of COPD: bronchodilators as mono- and combination therapies

Cited by 33 publications

References 46 publications

Pharmacological Characterization of Abediterol, a Novel Inhaled β2-Adrenoceptor Agonist with Long Duration of Action and a Favorable Safety Profile in Preclinical Models

Pharmacological Characterization of Abediterol, a Novel Inhaled β2-Adrenoceptor Agonist with Long Duration of Action and a Favorable Safety Profile in Preclinical Models

Emerging inhaled bronchodilators: an update

β‐Adrenoceptor Agonists and Asthma

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Product

Resources

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Pharmacological Characterization of Abediterol, a Novel Inhaled β₂-Adrenoceptor Agonist with Long Duration of Action and a Favorable Safety Profile in Preclinical Models

Pharmacological Characterization of Abediterol, a Novel Inhaled β₂-Adrenoceptor Agonist with Long Duration of Action and a Favorable Safety Profile in Preclinical Models