Ono Pharmaceutical Co., Ltd., Osaka.
J Toxicol Sci. 2010 Feb;35(1):97-100. doi: 10.2131/jts.35.97.
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.
在制药公司的药物开发过程中，光毒性评估变得越来越重要。已经开发出了用于评估化学物质光毒性潜力的体外和体内测试系统。在本研究中，我们使用 BALB/c 小鼠进行了体内光毒性试验。将司帕沙星、洛美沙星或喹啉衍生物口服给予小鼠，然后用模拟阳光照射，并评估耳朵的光毒性反应。司帕沙星和洛美沙星，但不是喹啉衍生物，已知会引起人类光刺激性。所有三种药物在 3T3 中性红摄取光毒性试验（3T3NRUPT）中均呈阳性反应。在体内试验中，司帕沙星和洛美沙星在小鼠中表现出阳性皮肤反应，但喹啉衍生物没有。在小鼠中的体内光毒性试验结果与这些药物在人类中的光毒性潜力一致。在小鼠中显示光毒性反应的最小有效剂量下，司帕沙星或洛美沙星的暴露水平与接受推荐治疗剂量的人类相当。
