Abstract
Background: Dextromethorphan (DM) is a non narcotic codeine analogue, widely used as antitusive agent. DM is active mostly centrally, but also in lung regions. DM was shown to be effective when given by inhalation in guinea pigs. Oral DM prior bronchoscopy is effective in reducing cough and dyspnea. The use of inhalation of DM could lead to faster beneficial effect of the drug, and to avoidance of oral preparation prior bronchoscopy.
Objectives: To define the toxicity of inhaled DM in a mouse model, using different doses and comparison with sham inhalation.
Methods: Female BALB/c mice, were divided to 4 groups exposed to increasing concentrations of DM solution: normal saline, 60, 90 and 360 mg/kg. Inhalation studies lasted ∼ 20 min/day, for 3 weeks. Blood analysis and complete histological evaluation were performed.
Results: There was no evidence of toxic effect in blood biochemical parameters, complete blood counts and gross pathology. Histological evaluation of the heart, kidneys, spleen, liver and pancreas was normal in all groups. However, abnormalities were found on lung pathology. In the high concentration group diffuse alveolar damage, alveolar hemorrhage, pulmonary congestion and severe bolus emphysema were shown, whereas in the low dose group only very mild emphysema was found. It is noteworthy that no signs of morbidity or behavioral changes were observed in all groups.
Conclusions: Very high dose Dextromethorphan inhalations have no biochemical or hemathological toxic effects, but may be toxic to the lungs. However, inhalation dose of 60 mg/kg seems to be safe. These data suggest that treatment with inhaled DM in lower doses may be safe and can be used in humans.
- © 2011 ERS