Background: We aimed to investigate whether dextromethorphan (DM), an antitussive, can improve the antifibrotic efficacy of pirfenidone in treating idiopathic pulmonary fibrosis, a fatal interstitial lung disease characterized by progressive and irreversible respiratory failure.
Methods: A bleomycin-induced mice pulmonary fibrosis study and an open label randomized clinical trial were performed to evaluate the effectiveness of pirfenidone combined with DM.
Results: In the animal study, pirfenidone combined with DM protected mice against bleomycin-induced pulmonary fibrosis with better capabilities than pirfenidone alone or DM alone indicated by lung histologic analysis and hydroxyproline levels. In the clinical study, pirfenidone plus DM markedly mitigated pulmonary functions (FEV1 and FVC) decline and ameliorated chest HRCT imaging scores (ground glass opacities and reticulation) of patients with IPF than pirfenidone alone at one year after administration. There were no significant differences in adverse reactions between pirfenidone-DM group and pirfenidone group.
Conclusions: DM significantly potentiates antifibrotic effectiveness of pirfenidone in a mouse IPF model and patients with IPF and does not increase side effects of pirfenidone.