title: Assessment of 8-methosypsoralen, lomefloxacin, sparfloxacin, and Pirfenidone phototoxicity in Long-Evans rats.
abstract: Phototoxicity has a strong impact on drug development. Although several animal models have been developed to quantitatively assess human risks, none have been validated for standardized use. In this study, we validated an in vivo phototoxicity model using Long-Evans (LE) rats treated with 4 well-known phototoxic drugs, namely 8-methoxypsoralen, lomefloxacin, sparfloxacin, and pirfenidone. Daily macroscopic observations of skin and eyes, ophthalmological examinations 4 days after dosing, and blood sampling for toxicokinetics (TKs) were performed after exposure of treated animals to ultraviolet, and dose-dependent eye and/or skin reactions were noted for all compounds. Margins of safety were calculated when possible and correlated well with known relative phototoxicity of the 4 compounds. We conclude that the present in vivo phototoxicity assay using LE rats with TK analysis can be used to quantitatively predict the risk of pharmaceutical phototoxicity in humans.
authors.affiliation: Research Division, Safety Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba, Japan.
authors.forename: Tamiko
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Research Division, Safety Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Satou
authors.affiliation: Research Division, Safety Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Satou
authors.affiliation: Research Division, Safety Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibata
authors.affiliation: Research Division, Safety Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Miwa
authors.affiliation: Research Division, Safety Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iwase
authors.affiliation: Research Division, Safety Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba, Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Research Division, Safety Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba, Japan.
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Nishida
authors.affiliation: Research Division, Safety Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba, Japan masutomi.naoya@mm.mt-pharma.co.jp.
authors.forename: Naoya
authors.initials: N
authors.lastname: Masutomi
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000378:metabolism; D017484:Dermatitis, Phototoxic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005123:Eye / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D005260:Female; D024841:Fluoroquinolones / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D011564:Furocoumarins / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D011728:Pyridones / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D020318:Rats, Long-Evans; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D001798:Blood Proteins; D024841:Fluoroquinolones; D011564:Furocoumarins; D011728:Pyridones; C051039:8-methylpsoralen; C093844:pirfenidone; C053091:lomefloxacin; C061363:sparfloxacin
keywords: 8-methoxypsoralen; Long-Evans rats; in vivo phototoxicity; lomefloxacin; pirfenidone; sparfloxacin