Source: Annual Congress 2012 - COPD treatments: efficacy and safety
Disease area: Airway diseases

Abstract

Introduction: Co-administration of a long-acting β-agonist with an anticholinergic is common clinical practice for the management of COPD, but there are concerns that systemic exposure to both drugs could cause undesirable pharmacodynamic effects on the heart.
Aims: To evaluate the cardiovascular safety of formoterol alone and in combination with aclidinium in conscious dogs.
Methods: Formoterol (1, 3, 10 μg/kg iv), aclidinium (50, 167 μg/kg iv) and formoterol+aclidinium (1+17, 3+50, 10+167 mg/kg iv) were administered to fasting, male Beagle dogs (n=4; 13–16 kg) in a 3-min perfusion. Each dog received each dose with >6-day washout. Electrocardiograms were recorded at baseline (for 1 h) and 24 h post-administration (for 90 min) and assessed for ventricular tachycardia (VT) and premature ventricular complexes (PVC).
Results: Formoterol alone showed a dose-dependent trend to induce VT. VT was observed in 0, 1 and 4 animals treated with formoterol 1, 3 and 10 μg/kg, respectively. Aclidinium alone (both doses) did not induce VT. The combination of formoterol+aclidinium resulted in VT in a similar number of animals as formoterol alone (2 and 3 animals with 3+50 and 10+167 μg/kg, respectively). Similar results were observed for PVC. At the highest doses of formoterol and aclidinium, the plasma concentrations corresponded to 32 and 4000 times those reported in human plasma after clinically relevant doses.
Conclusions: Addition of aclidinium does not alter the incidence or rate of formoterol-induced VT or PVC in dogs. These results suggest that aclidinium has no synergistic interaction on cardiac function with β-agonists.
This study was supported by Almirall S.A., Barcelona, Spain.

Rating:

Share or cite this content

Citations should be made in the following way:
A. Gavaldà, M. Vinyals, J. Aubets, J. Gras (Barcelona, Spain). Effect of formoterol alone and in combination with aclidinium on electrocardiograms in dogs. Eur Respir J 2012; 40: Suppl. 56, 2116

Member's Comments

No comment yet.

Related content which might interest you: Pharmacokinetic bioequivalence of inhaled CHF 1535 50/6 vs. the free combination of beclomethasone and formoterol in asthmatic children Source: Annual Congress 2011 - Drug delivery and pharmacokinetics I Year: 2011 Influence of higher than conventional doses of salbutamol or ipratropium bromide on bronchodilation induced by a regular treatment with tiotropium in patients suffering from stable COPD Source: Eur Respir J 2007; 30: Suppl. 51, 356s Year: 2007 24-hour bronchodilator efficacy of single doses of indacaterol in subjects with COPD, and comparison with formoterol Source: Annual Congress 2008 - Pathogenesis and treatment of asthma and COPD Year: 2008 Efficacy and safety of therapeutic and supratherapeutic doses of indacaterol compared to salmeterol and salbutamol, in mild-to-moderate asthma Source: Eur Respir J 2006; 28: Suppl. 50, 207s Year: 2006 Comparison of a combination of tiotropium and formoterol to salmeterol and fluticasone in moderate COPD Source: Eur Respir J 2005; 26: Suppl. 49, 14s Year: 2005 Effect of fluticasone and formoterol combination therapy on airway remodeling Source: Annual Congress 2011 - Models of disease and drug actions Year: 2011 24-hour bronchodilator efficacy of single doses of indacaterol in patients with persistent asthma, and comparison with formoterol Source: Annual Congress 2008 - New treatments for asthma Year: 2008 Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate following once daily inhalation as a fixed-dose combination in healthy subjects Source: International Congress 2019 – Clinical studies of asthma treatments Year: 2019 Bronchodilator effect of an inhaled combination therapy with salmeterol + fluticasone and formoterol + budesonide in patients with COPD Source: Eur Respir J 2002; 20: Suppl. 38, 386s Year: 2002 Safety and tolerability of high-dose formoterol via aerolizer and salbutamol via MDI in patients with mild-to-moderate COPD Source: Eur Respir J 2003; 22: Suppl. 45, 285s Year: 2003 Effect of fluticasone propionate/salmeterol plus tiotropium versus tiotropium on walking endurance in COPD Source: Eur Respir J 2013; 42: 539-541 Year: 2013 The additive effect of theophylline on a combination of formoterol and tiotropium in stable COPD Source: Eur Respir J 2006; 28: Suppl. 50, 212s Year: 2006 Comparative effects of formoterol monotherapy versus formoterol plus tiotropium on dynamic hyperinflation and exercise tolerance in COPD Source: Annual Congress 2009 - Influence of interventions and comorbidity on exercise performance Year: 2009 Effect of montelukast or salmeterol added to inhaled fluticasone on response to albuterol in children with exercise-induced bronchoconstriction Source: Annual Congress 2009 - Drug treatment of childhood asthma: the controversies and the issues Year: 2009 Bronchoprotective and anti-inflammatory effect of beclometasone dipropionate plus formoterol HFA fixed combination in asthmatic patients Source: Annual Congress 2009 - Aspects of uncontrolled asthma Year: 2009 Pharmacokinetics and pharmacodynamics of a new beclomethasone dipropionate and formoterol CFC-free fixed combination in healthy volunteers Source: Eur Respir J 2006; 28: Suppl. 50, 667s Year: 2006 Efficacy and safety of twice-daily aclidinium bromide compared with tiotropium and placebo in patients with moderate to severe COPD Source: Annual Congress 2010 - Regulation of airway hyperresponsiveness and bronchodilators Year: 2010 Pharmacokinetic evaluation of two HFA pMDI formulations of salmeterol xinafoate administered through a spacer in healthy subjects Source: Annual Congress 2011 - Drug delivery and pharmacokinetics II Year: 2011 LATE-BREAKING ABSTRACT: ENERGITO: Efficacy and safety of once-daily combined tiotropium + olodaterol versus twice-daily combined fluticasone propionate + salmeterol Source: International Congress 2015 – Emerging strategies for airway disease treatments Year: 2015 Comparison of spirometric efficacy of fluticasone/salmeterol plus tiotropium and tiotropium alone in moderate COPD Source: Annual Congress 2009 - New bronchodilators Year: 2009