Faster Onset of Bronchodilation with Formoterol than with Salmeterol in Patients with Stable, Moderate‐Severe Copd: Results of a Randomized, Double‐Blind Clinical Study

Kottakis, John; Cioppa, Giovanni Della; Creemers, Jacques; Greefhorst, Louis A.P.M.; Leclerc, Violette; Pistelli, Riccardo; Overend, Tim; Till, Denise; Rapatz, G.; Legros, Vincent; Bouros, Demosthenes; Siafakas, Nikolaos M.

doi:10.1155/2002/604092

Cited by 45 publications

(36 citation statements)

References 26 publications

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“…Accordingly, abediterol showed a fast onset of action relaxing human bronchi, not significantly different from that of formoterol. The results obtained with the reference compounds were consistent with the rates of onset of action in humans; formoterol was an effective bronchodilator within 5 min, salmeterol took 15 to 30 min to achieve significant bronchodilation over baseline, and indacaterol showed an onset of action faster than salmeterol (Kottakis et al, 2002;Sugihara et al, 2010). The onset of action of abediterol in preclinical models was in line with the first results in humans, where abediterol (5, 10, and 25 g), at 5 min postdose, significantly improved lung function compared with placebo (p Ͻ 0.0001) and salmeterol (p Ͻ 0.05) in patients with persistent asthma, suggesting a rapid onset of action .…”

Section: Discussionsupporting

confidence: 75%

“…The results obtained with salmeterol and formoterol were consistent with those reported previously (Jeppsson et al, 1992;Naline et al, 1994) where the compounds behaved as partial and full agonists, respectively. It is noteworthy that the different intrinsic efficacies of ␤ 2 -agonists measured in preclinical models have not translated in humans, where formoterol and salmeterol have reached comparable bronchodilator efficacies in both COPD and asthma (Kottakis et al, 2002). It has been suggested that ␤ 2 intrinsic efficacy, together with physicochemical properties, contribute to the clinical onset of bronchodilation of ␤ 2 -adrenoceptor agonists, with full agonists more prone to exhibit faster onset of action (Rosethorne et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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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

Aparici¹,

Gómez‐Angelats²,

Vilella³

et al. 2012

The Journal of Pharmacology and Experimental Therapeutics

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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: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

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

The Journal of Pharmacology and Experimental Therapeutics

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show abstract

“…These agents have been shown to reduce the need for rescue medication, improve symptoms and patient-related outcomes, and have a favourable safety profile. [50][51][52][53] Formoterol has a faster onset of action than salmeterol, 54,55 which may be relevant to some patients, especially for morning symptoms. The once-daily LABA indacaterol was approved in Europe in late 2009 for the treatment of COPD, and is discussed in the section "Emerging treatment options" below.…”

Section: Current Long-acting β2-agonists -Labasmentioning

confidence: 99%

Optimising pharmacological maintenance treatment for COPD in primary care

Jones

Østrem²

2010

Primary Care Respiratory Journal

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Chronic obstructive pulmonary disease (COPD) is a multi-faceted disease that is a major cause of morbidity and mortality worldwide, and is a significant burden in terms of healthcare resource utilisation and cost. Despite the availability of national and international guidelines, and effective, well-tolerated pharmacological treatments, COPD remains substantially under-diagnosed and under-treated within primary care. As COPD is both preventable and treatable there is an urgent need to raise the awareness and profile of the disease among primary care physicians and patients. Increasing evidence suggests that initiation of long-acting bronchodilator treatment at an early stage can significantly improve the patient's long-term health and quality of life (QoL). Recent large-scale trials in COPD have confirmed the longterm benefits of maintenance treatment with long-acting bronchodilators. A wide range of benefits have been shown in selected patient groups including improved lung function and QoL, reduced exacerbations and, in some studies, delayed disease progression and improved survival. In this review, we consider recent developments in our understanding of COPD, including current and emerging pharmacological treatment options, and identify steps for optimising early diagnosis and pharmacological treatment of COPD within the primary care environment.

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“…Fast onset of bronchodilatory action Kottakis et al (2002) compared formoterol 12 and 24 µg, as dry powder for oral inhalation, with dry powder salmeterol 50 and 100 µg in a single-dose, cross-over study in patients with partially reversible, moderately severe, stable COPD; ∆FEV 1 following a standard dose of salbutamol was not in excess of 12% of patient's predicted normal value. Median time to a 12% change from baseline FEV 1 value was 5 min with both formoterol doses and 10 min with both salmeterol doses.…”

Section: Formoterol For Copdmentioning

confidence: 99%

Formoterol in the management of chronic obstructive pulmonary disease

Steiropoulos

Τzouvelekis²,

Bouros

2008

COPD

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Abstract:Bronchodilators represent the hallmark of symptomatic treatment of Chronic Obstructive Pulmonary Disease (COPD). There are four categories of bronchodilators: anticholinergics, methylxanthines, short-acting β 2 -agonists, and long-acting β 2 -agonists such as formoterol. Signifi cant research has been performed to investigate the effi cacy, safety and tolerability of formoterol in the therapeutic fi eld of COPD. Formoterol exhibits a rapid onset of bronchodilation similar to that observed with salbutamol, yet its long bronchodilatory duration is comparable to salmeterol. In addition, formoterol presents with a clear superiority in lung function improvement compared with either ipratropium bromide or oral theophylline, while its effi cacy improves when administered in combination with ipratropium. Formoterol has been shown to better reduce dynamic hyperinfl ation, which is responsible for exercise intolerance and dyspnea in COPD patients, compared with other bronchodilators, whereas it exerts synergistic effect with tiotropium. Moreover, formoterol reduces exacerbations, increases days free of use of rescue medication and improves patients' quality of life and disease symptoms. Formoterol has a favorable safety profi le and is better tolerated than theophylline. Collectively, data extracted from multicenter clinical trials support formoterol as a valid therapeutic option in the treatment of COPD.

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Faster Onset of Bronchodilation with Formoterol than with Salmeterol in Patients with Stable, Moderate‐Severe Copd: Results of a Randomized, Double‐Blind Clinical Study

Abstract: Formoterol is associated with a faster onset of bronchodilation than salmeterol in patients with COPD.

Cited by 45 publications

References 26 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

Optimising pharmacological maintenance treatment for COPD in primary care

Formoterol in the management of chronic obstructive pulmonary disease

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