Abstract |
Pirfenidone (PFD), an idiopathic pulmonary fibrosis drug, has phototoxic risk in clinical use, although its detailed mechanisms for the phototoxicity have never been fully elucidated. In the present study, the photochemical properties and in vitro phototoxicity of PFD were evaluated with a focus on ultraviolet absorption, reactive oxygen species (ROS) generation, photodynamic lipid peroxidation, and DNA photocleavage. To clarify the in vivo phototoxic behavior of PFD, photoirritation and pharmacokinetic characteristics were also assessed in rats after its oral administration. There was marked generation of singlet oxygen and superoxide from PFD upon exposure to simulated sunlight, suggesting its high photoreactivity and phototoxic potential. Photobiochemical studies demonstrated the potent in vitro photoirritation of PFD, but not its photogenotoxic risk. Pharmacokinetic profiling and in vivo phototoxicity testing on PFD at a dose of 160mg/kg suggested that highly concentrated PFD in the skin might cause phototoxic skin reactions in rats, whereas PFD at 30mg/kg was far less phototoxic, possibly due to the limited skin deposition. From these findings, a high dose of orally administered PFD might cause phototoxic skin responses, possibly via a ROS-mediated photoirritant pathway.
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Authors | Yoshiki Seto, Ryo Inoue, Masashi Kato, Shizuo Yamada, Satomi Onoue |
Journal | Journal of photochemistry and photobiology. B, Biology
(J Photochem Photobiol B)
Vol. 120
Pg. 44-51
(Mar 05 2013)
ISSN: 1873-2682 [Electronic] Switzerland |
PMID | 23419534
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier B.V. All rights reserved. |
Chemical References |
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Topics |
- Administration, Oral
- Animals
- Male
- Photobiology
- Photochemical Processes
- Pyridones
(adverse effects, chemistry, pharmacokinetics)
- Radiography
- Rats
- Rats, Sprague-Dawley
- Safety
- Skin
(diagnostic imaging, drug effects)
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