An update on the efficacy and safety of aclidinium bromide in patients with COPD

Abstract

Aclidinium is a potent and selective muscarinic antagonist, which interacts rapidly with muscarinic receptors and shows subnanomolar affinity for the five human muscarinic receptors (M1–M5); its association rate for the M3 receptor is similar to that of ipratropium and 2.6 times faster than that of tiotropium. Aclidinium dissociates slightly faster from M2 and M3 receptors than tiotropium but much more slowly than ipratropium. A potent bronchodilatory activity has been observed after inhaled administration of aclidinium. Aclidinium undergoes rapid hydrolysis in the plasma into two major compounds, the alcohol (LAS34823) and the carboxylic acid (LAS34850) metabolites, resulting in low and transient systemic exposure to the active drug. The two major metabolites show no significant affinity for human muscarinic receptors. A potent bronchodilatory activity has been observed after inhaled administration of aclidinium. Clinical trials have provided evidence of sustained bronchodilation similar to that observed with tiotropium. Trial results have confirmed the positive safety profile of aclidinium, particularly in terms of a very low propensity to cause anticholinergic adverse events. Aclidinium is now moving to phase III clinical development for chronic obstructive pulmonary disease (COPD).