Seto Yoshiki, Hosoi Kazuhiro, Takagi Hironori, Nakamura Kazuichi, Kojima Hajime, Yamada Shizuo, Onoue Satomi
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Japan.
Curr Drug Saf. 2012 Apr;7(2):140-8. doi: 10.2174/157488612802715726.
Drug-induced phototoxicity is elicited after exposure of the skin and/or eyes to topically or systemically administered pharmaceutical substances, followed by exposure to sunlight. This undesirable side effect is one of the impediments in drug discovery and development, and substantial efforts have been made to avoid drug-induced phototoxic reactions. To evaluate the phototoxic potential of compounds, effective methodologies have been developed over the past few years, and screening strategies have also been proposed for predicting in vivo phototoxic reactions. European and American regulatory agencies have published guidelines for predicting and avoiding drug-induced phototoxicity in an early phase of drug discovery. The guidelines have indicated the requirements for assessing the photosafety of chemicals on the basis of their photochemical behaviors and have recommended some phototoxic assessment tools for aiding new drug development. A number of phototoxic screening systems have also been proposed on the basis of the pathogenesis of drug-induced phototoxicity, and some of them have already been applied to the phototoxic evaluation of new drug entities in drug discovery and development. The present review aims to summarize the current status of research tools, screening strategy and regulations for evaluating the photosafety of new drug candidates and to introduce our thoughts on the phototoxic risk assessments of compounds.
药物诱导的光毒性是在皮肤和/或眼睛局部或全身接触给药的药物物质后，再暴露于阳光下引发的。这种不良副作用是药物研发中的障碍之一，人们已做出大量努力来避免药物诱导的光毒性反应。为评估化合物的光毒性潜力，在过去几年中已开发出有效的方法，还提出了用于预测体内光毒性反应的筛选策略。欧美监管机构已发布在药物研发早期预测和避免药物诱导光毒性的指南。这些指南指出了根据化学物质的光化学行为评估其光安全性的要求，并推荐了一些用于辅助新药开发的光毒性评估工具。基于药物诱导光毒性的发病机制，也提出了许多光毒性筛选系统，其中一些已应用于新药研发中对新化学实体的光毒性评估。本综述旨在总结评估新药候选物光安全性的研究工具、筛选策略和法规的现状，并介绍我们对化合物光毒性风险评估的看法。
