Communication to the Editor : Possible Involvement of Pirfenidone Metabolites in the Antifibrotic Action of a Therapy for Idiopathic Pulmonary Fibrosis

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  • Togami Kohei
    Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy Department of Biopharmaceutics, School of Pharmaceutical Science, Ohu University
  • Kanehira Yukimune
    Department of Biopharmaceutics, School of Pharmaceutical Science, Ohu University
  • Tada Hitoshi
    Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy Department of Biopharmaceutics, School of Pharmaceutical Science, Ohu University

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  • Possible Involvement of Pirfenidone Metabolites in the Antifibrotic Action of a Therapy for Idiopathic Pulmonary Fibrosis

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Pirfenidone (PFD) is the first and only clinically used antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). This study evaluated the antifibrotic effects of two metabolites of PFD, 5-hydroxypirfenidone (PFD-OH) and 5-carboxypirfenidone (PFD-COOH), on WI-38 cells in an in vitro lung fibroblast model. The inhibitory effects of PFD-OH and PFD-COOH on transforming growth factor-β1 (TGF-β1)-induced collagen synthesis in WI-38 cells were evaluated by measuring intracellular hydroxyproline, a major component of the protein collagen. PFD-OH and PFD-COOH at 300 and 1000 µM concentrations significantly decreased the TGF-β1-induced hydroxyproline content in WI-38 cells. These results indicate that PFD-OH and PFD-COOH have antifibrotic activities, which inhibit collagen synthesis in fibroblasts. This study suggests that the concentrations of PFD and its metabolites should be considered in clinical therapy for IPF.

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