Comparative study of skin phototoxicity with three drugs by an in vivo mouse model.
Photosafety evaluation is becoming important during the drug development process in pharmaceutical companies. Both in vitro and in vivo test systems have been developed for the evaluation of phototoxic potential of chemicals. In the present study, we conducted an in vivo phototoxicity test using BALB/c mice. The mice were treated with sparfloxacin, lomefloxacin, or a quinoline derivative orally followed by the irradiation of simulated sunlight, and resulting phototoxic reactions of the ears were assessed. Sparfloxacin and lomefloxacin, but not the quinoline derivative, are well known to cause photoirritation in humans. All three drugs exhibited positive reaction in the 3T3 neutral red uptake phototoxicity test (3T3 NRU PT). In the in vivo test, sparfloxacin and lomefloxacin exhibited positive skin reaction in mice, but the quinoline derivative did not. The results of in vivo phototoxicity test in the mice coincided with phototoxic potential of these drugs in humans. The exposure levels of sparfloxacin or lomefloxacin at the minimum effective dose that exhibited phototoxic reaction in the mice were comparable with those in humans treated with the recommended therapeutic dose.
Matsumoto
Norihito
N
Ono Pharmaceutical Co., Ltd., Osaka. no.matsumoto@ono.co.jp
Akimoto
Akira
A
Kawashima
Hiroyuki
H
Kim
Soonih
S
D016475:3T3 Cells / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D000995:Antitubercular Agents / Q000493:pharmacokinetics / Q000633:toxicity; D017484:Dermatitis, Phototoxic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004431:Ear, External / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D017319:Photosensitizing Agents / Q000145:classification / Q000493:pharmacokinetics / Q000633:toxicity*; D011804:Quinolines / Q000493:pharmacokinetics / Q000633:toxicity; D011859:Radiography; D012867:Skin / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D014466:Ultraviolet Rays
D000995:Antitubercular Agents; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D011804:Quinolines; C053091:lomefloxacin; C061363:sparfloxacin