Pharmacology and Clinical Efficacy of Erdosteine in Chronic Obstructive Pulmonary Disease

Maurizio Moretti

Disclosures

Expert Rev Resp Med. 2007;1(3):307-316. 

In This Article

Clinical Investigations

The free sulfhydryl group of metabolite I breaks the disulfide bridges of mucus glycoproteins, resulting in reduced sputum physical properties in patients with acute and chronic mucus hypersecretion. The effect of erdosteine on mucus rheological properties was evaluated in patients with exacerbation of COPD.[24] Patients receiving erdosteine had statistically significant reduction in sputum viscosity both at day 3 and at the end of the treatment compared with the placebo group. Similar results were obtained on sputum elasticity.

The efficacy of erdosteine on sputum rheological parameters was also evaluated in patients with clinically stable COPD.[10] A statistically significant reduction in sputum viscosity was observed in the erdosteine group, both when compared with pretreatment values and in comparison with placebo. Patients receiving erdosteine showed a significant decrease in fucose and dry macromolecular weight, markers of mucus glycoprotein content.

A mucolytic drug that reduces mucus rheological properties should also improve mucociliary clearance. In fact, the effect of erdosteine on mucociliary transport assessed by a modified broncho-fiber-optic technique was shown in a double-blind, placebo-controlled study in CB patients receiving 8-day treatment with placebo or erdosteine 900 mg/day.[25] Erdosteine significantly improved mucociliary transport compared with placebo. These data confirm the positive effect of erdosteine on ciliary movement in animal studies.[26]

Several studies have also demonstrated the effectiveness of erdosteine in reducing the volume of bronchial secretions during exacerbation of CB.[24,27]

Clinical studies showed that erdosteine increases sputum antibiotic concentrations in patients with acute exacerbations of CB and COPD.[28,29] A double-blind, placebo-controlled clinical trial evaluated the penetration of amoxycillin into the sputum after single and multiple oral antibiotic doses administered either alone or in combination with erdosteine.[28] Significant higher amoxycillin concentration was found in sputum but not in serum of patients treated with amoxycillin plus erdosteine; the effect persisted for a longer period. Sputum viscosity and body temperature also declined at a faster rate in the erdosteine group than in the control group. The authors argued that the mucolytic activity of erdosteine could improve amoxycillin diffusion in bronchial secretions.

The synergism of erdosteine with antibiotic therapy has been studied in several clinical trials in adult and pediatric patients with different antibiotics, such as amoxycillin,[29,30] ciprofloxacin[31] and ampicillin.[32] These studies demonstrate that the addition of erdosteine to different classes of antibiotics in acute infections of lower respiratory tract can induce a faster improvement of clinical symptoms compared with the antibiotic treatment alone.

Dal Negro et al. assessed the effect of 10-day treatment with erdosteine at a dose of 900 mg/day on ROS in peripheral blood and chemotactic cytokines (IL-6 and IL-8) in bronchial secretions of stable COPD patients who were active smokers.[33] Erdosteine significantly decreased the serum concentrations of ROS and proinflammatory cytokines. The decrease of ROS was significant after only 4 days of treatment and was maintained up to day 10, whereas lower cytokine levels were seen starting from day 7. The results of this study have been confirmed by a double-blind, placebo-controlled trial in stable COPD patients receiving erdosteine at the dose of 600 mg/day; interestingly, the study showed a reduction of sputum 8-isoprostane, a product of lipid peroxidation, only in the erdosteine group, which was statistically significant after 10 days of treatment.[34] These data show that erdosteine inhibits the oxygen radicals and the subsequent inflammation. These positive effects correlate with erdosteine's direct antioxidative effect and/or increased antioxidative cellular mechanisms.

A study also evaluated the markers of bronchial inflammation in patients with clinically stable COPD.[10] In the group receiving erdosteine, the concentrations of bronchial inflammation markers (i.e., albumin, IgG and DNA) decreased after 2 weeks of treatment compared with the placebo group. In the same group, a slight increase in sputum total IgA, lactoferrin and lysozyme was observed. These findings demonstrate a reduction of the inflammatory process of bronchial mucosa.

Antioxidative Activity in Healthy Smokers. In a placebo-controlled, double-blind clinical study, healthy smokers received erdosteine 175-mg twice daily for 1 month, without quitting the smoking habit.[35] In this study, the authors investigated the acute effect of smoking a single cigarette on serum TBARS marker of membrane lipid peroxidation and cellular injury. TBARS concentrations decreased 5 and 30 min after smoking compared with presmoking concentrations in the erdosteine group; the difference with the placebo group was statistically significant. This protective effect of erdosteine after exposure to an oxidative stress factor suggests that erdosteine might be a preventive agent for smoking-induced lipid peroxidation.

Erdosteine also protects α-1 antitrypsin from inactivation due to cigarette smoke[36] and increases glutathione plasma level in CB patients.[37]

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