Abstract
Introduction: 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.
| Original language | English |
|---|---|
| Pages (from-to) | 563-577 |
| Number of pages | 15 |
| Journal | Expert Opinion on Drug Discovery |
| Volume | 13 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 3 2018 |
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Keywords
- Aclidinium bromide
- bronchodilators
- chronic obstructive pulmonary disease
- long-acting muscarinic receptor antagonists
- pharmacotherapy
ASJC Scopus subject areas
- Drug Discovery
Cite this
The discovery and development of aclidinium bromide for the treatment of chronic obstructive pulmonary disease. / Malerba, Mario; Radaeli, Alessandro; Santini, Giuseppe; Morjaria, Jaymin; Mores, Nadia; Mondino, Chiara; Macis, Giuseppe; Montuschi, Paolo.
In: Expert Opinion on Drug Discovery, Vol. 13, No. 6, 03.06.2018, p. 563-577.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The discovery and development of aclidinium bromide for the treatment of chronic obstructive pulmonary disease
AU - Malerba, Mario
AU - Radaeli, Alessandro
AU - Santini, Giuseppe
AU - Morjaria, Jaymin
AU - Mores, Nadia
AU - Mondino, Chiara
AU - Macis, Giuseppe
AU - Montuschi, Paolo
PY - 2018/6/3
Y1 - 2018/6/3
N2 - Introduction: 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.
AB - Introduction: 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.
KW - Aclidinium bromide
KW - bronchodilators
KW - chronic obstructive pulmonary disease
KW - long-acting muscarinic receptor antagonists
KW - pharmacotherapy
UR - http://www.scopus.com/inward/record.url?scp=85044945432&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044945432&partnerID=8YFLogxK
U2 - 10.1080/17460441.2018.1455661
DO - 10.1080/17460441.2018.1455661
M3 - Article
AN - SCOPUS:85044945432
VL - 13
SP - 563
EP - 577
JO - Expert Opinion on Drug Discovery
JF - Expert Opinion on Drug Discovery
SN - 1746-0441
IS - 6
ER -