Nedderman Angus N R, Wright Pat
Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Sandwich, Kent, CT13 9NJ, UK.
Bioanalysis. 2010 Jul;2(7):1235-48. doi: 10.4155/bio.10.71.
The publication of the US FDA MIST guidance document in 2008 reignited the debate around the most appropriate strategies to underwrite metabolite safety for novel compounds. Whilst some organizations have suggested that the guidelines necessitate a paradigm shift to more thorough metabolite analysis during early development, an evaluation of historical practices shows that the principles of the guidelines have always largely underpinned metabolism studies within the pharmaceutical industry. Therefore, it is argued that existing practices, when coupled to appropriate emerging analytical tools and a case-by-case consideration of the relevance of the generated metabolism data in terms of structure, physicochemisty, abundance and activity, represent a fit-for-purpose approach to metabolite-safety assessments.
2008年美国食品药品监督管理局（US FDA）的《MIST指导文件》发布，重新引发了关于为新化合物确定代谢物安全性的最适当策略的争论。虽然一些组织认为该指南需要在早期开发过程中进行范式转变，以进行更全面的代谢物分析，但对历史实践的评估表明，该指南的原则在很大程度上一直是制药行业代谢研究的基础。因此，有人认为，现有实践结合适当的新兴分析工具，并根据结构、物理化学性质、丰度和活性对所生成的代谢数据的相关性进行逐案考虑，代表了一种适用于代谢物安全性评估的方法。
