title: Antifibrotic activities of pirfenidone in animal models.
abstract: Pirfenidone is an orally active small molecule that has recently been evaluated in large clinical trials for the treatment of idiopathic pulmonary fibrosis, a fatal disease in which the uncontrolled deposition of extracellular matrix leads to progressive loss of lung function. This review describes the activity of pirfenidone in several well-characterised animal models of fibrosis in the lung, liver, heart and kidney. In these studies, treatment-related reductions in fibrosis are associated with modulation of cytokines and growth factors, with the most commonly reported effect being reduction of transforming growth factor-β. The consistent antifibrotic activity of pirfenidone in a broad array of animal models provides a strong preclinical rationale for the clinical characterisation of pirfenidone in pulmonary fibrosis and, potentially, other conditions with a significant fibrotic component.
authors.affiliation: InterMune Inc., Brisbane, CA, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Schaefer
authors.forename: D W
authors.initials: DW
authors.lastname: Ruhrmund
authors.forename: L
authors.initials: L
authors.lastname: Pan
authors.forename: S D
authors.initials: SD
authors.lastname: Seiwert
authors.forename: K
authors.initials: K
authors.lastname: Kossen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011728:Pyridones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; D011728:Pyridones; D016212:Transforming Growth Factor beta; C093844:pirfenidone