The discovery and development of aclidinium bromide for the treatment of chronic obstructive pulmonary disease.
Bronchodilators, including long-acting muscarinic receptor antagonists (LAMAs), are a mainstay of the pharmacological treatment of chronic obstructive pulmonary disease (COPD). LAMAs act as bronchodilators principally by antagonizing airway smooth muscle cells M3 muscarinic receptors. Aclidinium bromide is a twice-daily LAMA which was developed to improve on the efficacy and/or safety of previous LAMAs. Area covered: Herein, the authors present the pharmacotherapeutic role of aclidinium in COPD and point out unmet need in this research area. The following aspects are covered: a) the discovery and medicinal chemistry of aclidinium bromide; b) an overview of the market; c) its mechanism of action; d) its pharmacokinetic/pharmacodynamic profile derived from pre-clinical studies; e) the clinical studies which led to its licensing; f) the evidence from meta-analyses; g) the aclidinium/formoterol fixed dose combination for COPD and h) priorities in this area of research. Expert opinion: Aclidinium bromide has the pharmacological properties, safety and efficacy profile and inhaler characteristics which makes it a valuable therapeutic option for pharmacological management of patients with COPD. Due to its rapid biotransformation into inactive metabolites, aclidinium is potentially one of the safest LAMAs. Further head-to-head randomized clinical trials are required to define efficacy and safety of aclidinium when compared to once-daily LAMAs. The clinical relevance of airway anti-remodeling effects of aclidinium has to be defined.
['Malerba|Mario|M|', 'Radaeli|Alessandro|A|', 'Santini|Giuseppe|G|', 'Morjaria|Jaymin|J|', 'Mores|Nadia|N|', 'Mondino|Chiara|C|', 'Macis|Giuseppe|G|', 'Montuschi|Paolo|P|']
D000280:Administration, Inhalation D000818:Animals D001993:Bronchodilator Agents D003692:Delayed-Action Preparations D000076722:Drug Development D006801:Humans D018727:Muscarinic Antagonists D029424:Pulmonary Disease, Chronic Obstructive D014326:Tropanes
Aclidinium bromide chronic obstructive pulmonary disease bronchodilators long-acting muscarinic receptor antagonists pharmacotherapy