Effect of pirfenidone on the development of pellagra-related nausea in mice

Abstract

<b>Introduction:</b> Pirfenidone, an anti-fibrotic drug used to treat idiopathic pulmonary fibrosis, causes side effects, such as nausea and photosensitivity. Although some side effects appear pellagra-like, their association with pirfenidone is poorly understood. Here, we evaluated the effect of pirfenidone on the development of pellagra-related nausea using a newly established mouse model. <b>Aims and objectives:</b> We investigated the role of pirfenidone in the development of pellagra-related nausea. <b>Methods:</b> Mice maintained on normal and niacin-deficient diets were administered pirfenidone (1.0 and 3.0 mg/mg/animal, twice daily, 5 days), and the resulting nausea was evaluated based on their pica behavior. The urinary metabolite levels were analyzed using liquid chromatography coupled with mass spectrometry. <b>Results:</b> Pirfenidone-induced pica behavior was observed in mice that were fed a niacin-deficient diet but not in those on a normal diet. Urinary metabolites such as 2-PY and 4-PY were significantly reduced in the mice treated with pirfenidone compared to those without pirfenidone. Further, niacin treatment prevented pica behavior in this mouse model. <b>Conclusions:</b> Pirfenidone may cause pellagra or pellagra-like symptoms such as nausea and photosensitivity. Further studies are needed to investigate whether niacin prevents these adverse effects in IPF patients with pirfenidone.