Multifaceted Beneficial Effects of Erdosteine: More than a Mucolytic Agent

Abstract

Erdosteine is a drug approved for the treatment of acute and chronic pulmonary diseases, originally developed as a mucolytic agent. It belongs to the thiol-based family of drugs that are known to also possess potentially important antioxidant and anti-inflammatory properties, and exhibit antibacterial activity against a variety of medically important bacterial species. Erdosteine is a prodrug that is metabolized to the ring-opening compound metabolite M1 (MET 1), which has mucolytic properties. Experimental studies have documented that erdosteine prevents or reduces lung tissue damage induced by oxidative stress and, in particular, that Met 1 also regulates reactive oxygen species production. The RESTORE study, which has been the only trial that investigated the effects of a thiol-based drug in chronic obstructive pulmonary disease (COPD) frequent exacerbators, documented that erdosteine significantly reduces the risk of acute exacerbations of COPD (AECOPDs), shortens their course, and also decreases the risk of hospitalization from COPD. The preventive action of erdosteine on AECOPDs was not affected by the presence or absence of inhaled corticosteroids (ICSs) or blood eosinophil count. These findings clearly contrast with the Global Initiative for Chronic Obstructive Lung Disease strategy's approach to use erdosteine only in those COPD patients not treated simultaneously with an ICS. Furthermore, they support the possibility of using erdosteine in a step-down approach that in COPD is characterized by the withdrawal of the ICS.

Fig. 1

Chemical structure of erdosteine (a) and Met I (b)

Fig. 2

Principal signalling pathways caused by reactive oxyden species (ROS) production

Fig. 3

Comparative analysis of the effect of the drugs on E. coli adhesiveness. The findings are expressed as percentages of the final mean values versus controls (modified from Braga et al. [20])

Fig. 4

Effects of sub-MICs of clarithromycin alone (solid lines) and in combination with Met I (dashed lines) 5 μg/mL (a) and 10 μg/mL (b) on S. aureus adhesiveness (modified from Braga et al. [21])