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Pirfenidone is a pyridine-derived, double-ringed molecule that has a number of biologic effects including anti-inflammatory and antifibrotic properties in rodent models of acute lung injury and fibrosis, in addition to scavenging reactive oxygen species. These effects are clinically relevant, because idiopathic pulmonary fibrosis (IPF) is a progressive and increasingly prevalent disease characterized by diffuse lung scarring due to alveolar epithelial cell injury, which typically leads to death 3-5 years after diagnosis. No proven therapy for IPF exists, and many IPF patients eventually require lung transplantation, making the need for pharmacologic therapy great. Pirfenidone is rapidly distributed in body water and metabolized by the liver. Several clinical trials have tested pirfenidone in patients with IPF and found it well-tolerated with acceptable side effects. Pirfenidone in clinical trials has been found to improve progression-free survival and pulmonary function of IPF patients. Although the specific mechanism accounting for its benefits is not known, pirfenidone decreases collagen synthesis and fibroblast prolifera- tion, and it may down-regulate inflammation by virtue of its effects on mitogen-activated protein kinases. Pirfenidone has gained regulatory approval for marketing in Japan and in the European Union. It could prove to be a useful therapeutic agent for patients with IPF.

Development and utility of pirfenidone in the treatment of idiopathic pulmonary fibrosis: review of preclinical science and recent clinical trials