The discovery and development of aclidinium bromide for the treatment of chronic obstructive pulmonary disease

Mario Malerba, Alessandro Radaeli, Giuseppe Santini, Jaymin Morjaria, Nadia Mores, Chiara Mondino, Giuseppe Macis, Paolo Montuschi

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)563-577
Number of pages15
JournalExpert Opinion on Drug Discovery
Volume13
Issue number6
DOIs
Publication statusPublished - Jun 3 2018

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Muscarinic Antagonists
Muscarinic Receptors
Chronic Obstructive Pulmonary Disease
Bronchodilator Agents
Pharmacology
Safety
Therapeutics
Muscarinic M3 Receptors
Airway Remodeling
Pharmaceutical Chemistry
Nebulizers and Vaporizers
Expert Testimony
Licensure
Biotransformation
Research
Smooth Muscle Myocytes
Meta-Analysis
aclidinium bromide
Randomized Controlled Trials
Pharmacokinetics

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 journalArticle

Malerba, Mario ; Radaeli, Alessandro ; Santini, Giuseppe ; Morjaria, Jaymin ; Mores, Nadia ; Mondino, Chiara ; Macis, Giuseppe ; Montuschi, Paolo. / The discovery and development of aclidinium bromide for the treatment of chronic obstructive pulmonary disease. In: Expert Opinion on Drug Discovery. 2018 ; Vol. 13, No. 6. pp. 563-577.
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