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

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Abstract

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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