Efficacy of erdosteine 900 versus 600 mg/day in reducing oxidative stress in patients with COPD exacerbations: Results of a double blind, placebo-controlled trial.

Abstract

BACKGROUND:

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with increased airway and systemic inflammation. There is evidence that erdosteine accelerates recovery from AECOPD by reducing airway inflammation.

AIM:

To investigate the dose-dependent antioxidant/anti-inflammatory activity of erdosteine in COPD patients.

METHODS:

In this single-centre, double blind, double dummy study, patients with mild-to-moderate COPD (GOLD stage II-III), were randomised to receive either placebo or two dosages of oral erdosteine (300 mg tid or 300 mg bid + 1 capsule of indistinguishable placebo) for 28 days in addition to their standard treatment. Primary variables were plasma reactive oxygen species (ROS) and 8-isoprostane levels, while secondary variable was lung function (FEV1; FEV1/FVC; FEV1 short-term reversibility), all assessed in baseline; every two weeks during the study, and one week after the end of the study.

RESULTS:

Baseline demographic characteristics, plasma ROS and 8-isoprostane levels and lung function were not significantly different in the 24 eligible patients (14 males, aged 38-75 years). At 2 weeks, there was a dose-dependent decrease in ROS in the erdosteine groups. By week 4 there were significant differences in ROS levels compared to baseline between patients receiving 900 mg/day (p < 0.003) and those receiving 600 mg/day (p < 0.04). This effect continued in the follow-up week (p < 0.021). Erdosteine also lowered 8-isoprostane plasma levels after 4 weeks (p < 0.01), and this effect lasted over the post-treatment week. Moreover, % FEV1 reversibility after salbutamol 400 mcg obtained after a 4 -week treatment of erdosteine 900 mg/day was significantly higher than that obtained after 600 mg/day (p < 0.01). Erdosteine was well tolerated and no treatment-related adverse event was reported.

CONCLUSIONS:

Results confirm the antioxidant dose- and time-dependent activity of erdosteine, and support the utility of including erdosteine it in the therapeutic strategy for the prevention and treatment of oxidative stress-induced inflammation, which frequently leads to AECOPD occurrence.

• Authors: R W Dal Negro, M Visconti, P Turco
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 33 Pg. 47-51 (Aug 2015) ISSN: 1522-9629 [Electronic] England
• PMID: 26116425 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antioxidants
• Bronchodilator Agents
• Expectorants
• Reactive Oxygen Species
• Thioglycolates
• Thiophenes
• erdosteine
• Albuterol

Topics

• Administration, Oral
• Adult
• Aged
• Albuterol (pharmacology)
• Antioxidants (administration & dosage, pharmacology)
• Bronchodilator Agents (pharmacology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Expectorants (administration & dosage, pharmacology, therapeutic use)
• Female
• Follow-Up Studies
• Forced Expiratory Volume (drug effects)
• Humans
• Inflammation (drug therapy, physiopathology)
• Male
• Middle Aged
• Oxidative Stress (drug effects)
• Pulmonary Disease, Chronic Obstructive (drug therapy, physiopathology)
• Reactive Oxygen Species (metabolism)
• Thioglycolates (administration & dosage, pharmacology, therapeutic use)
• Thiophenes (administration & dosage, pharmacology, therapeutic use)