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Photosafety assessments on pirfenidone: Photochemical, photobiological, and pharmacokinetic characterization

Paper ID Volume ID Publish Year Pages File Format Full-Text
30627 44494 2013 8 PDF Available
Title
Photosafety assessments on pirfenidone: Photochemical, photobiological, and pharmacokinetic characterization
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 160 mg/kg suggested that highly concentrated PFD in the skin might cause phototoxic skin reactions in rats, whereas PFD at 30 mg/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.

► Photochemical properties and in vitro phototoxic risk of pirfenidone were evaluated. ► Pirfenidone might be photoreactive and photoirritant, but not photogenotoxic. ► High dose of orally administered PFD might cause phototoxic skin responses in vivo.

Keywords
Phototoxicity; Pirfenidone; Reactive oxygen species; Pharmacokinetic
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Photosafety assessments on pirfenidone: Photochemical, photobiological, and pharmacokinetic characterization
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 120, 5 March 2013, Pages 44–51
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us