小分子药物研发中代谢产物非临床研究的关注要点

Main concerns about nonclinical studies of metabolites during development of small-molecule drugs

小分子药物在实验动物种属和人体中的代谢特征可能存在差异,在人体中可能存在特有的或高水平的代谢产物。如果在非临床安全性试验中这些代谢产物未被鉴定或充分评估,可能将不能充分保障人体用药的安全性。根据具体情况,可能需要对这些代谢产物进行非临床安全性研究。本文阐述了国际人用药品注册技术要求协调会和监管机构相关指导原则的要求,并结合案例分析,探讨小分子药物研发中代谢产物非临床研究的关注要点。

Small molecule drugs may have different metabolic profiles in experimental animal species and in humans,and there are cases which some metabolites are identified only in humans or present at higher plasma concentrations in humans than in the animal species.When these metabolites have not been identified or adequately evaluated in non-clinical studies,it may be insufficient to ensure the safety use of drugs in humans.Nonclinical safety studies of the metabolites may be warranted base on case-by-case.This artical described recommendations of relevant guidelines of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use and various regulatory agencies,and discussed major concerns about nonclinical studies of metabolites during small molecule drugs development,combining case analysis.