Safety Versus Toxicity of Inhaled Dextromethorphan in the Mice: Hematological, Biochemical and Histological approaches

Safety Versus Toxicity of Inhaled Dextromethorphan in Hematological, Biochemical and Histological approaches. Pulm Respir 5: 021. Abstract Background: Dextromethorphan (DM), an antitussive, was previ- ously proven to effectively reduce cough when pre-medicating patients before bronchoscopy. The purpose of this study was to evalu- ate the safety vs. toxicity of inhaled DM in animals. Methods: Female BALB/c mice were exposed to repeatedly admin- istered aerosolized DM of 1 or 10mg/kg (safety phase) or 1, 60 or 360mg/kg (toxicological phase). Control animals were exposed to 0.9% NS-based aerosol. At the end of each series of treatments histological, hematological and toxicological analyses were performed on collected samples. Results: Treatment-related microscopic lesions were observed only in the lungs, ranging from negligible to severe and diffused alveolar damage (DAD). These findings were detected 5 days after the end of 5-session trials of the 10mg/kg dose and 24 h after 15 inhalations of the toxic doses, respectively. The 1mg/kg dose was innocuous. No damage was detected after single sessions; nor were there biochemical or hematological pathologies detected in any of the groups. Conclusion: A direct correlation may exist between DM dosing and the resulting severity of lung histopathological damage. Additional variables inducing it were multiplicity of inhalations and the time elapsing between the last session of inhalation and the pathological findings of DAD. The single dose of 1mg/kg DM, that is above the clinically accepted DM oral dose, proved safe in the tested animals.