• Biol. Pharm. Bull. · Jan 2013

    Possible involvement of pirfenidone metabolites in the antifibrotic action of a therapy for idiopathic pulmonary fibrosis.

    • Kohei Togami, Yukimune Kanehira, and Hitoshi Tada.
    • Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy.
    • Biol. Pharm. Bull. 2013 Jan 1; 36 (10): 1525-7.

    AbstractPirfenidone (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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