Chen Minjun, Borlak Jürgen, Tong Weida
Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
Expert Rev Gastroenterol Hepatol. 2014 Sep;8(7):721-3. doi: 10.1586/17474124.2014.922871. Epub 2014 May 23.
Drug-induced liver injury (DILI) is a major challenge for the pharmaceutical industry, regulatory authorities, and clinicians. It is usually categorized into 'intrinsic' and 'idiosyncratic', but DILI caused by most drugs is of an idiosyncratic nature and usually cannot be predicted from the regulatory required animal toxicity studies. Unfortunately, some individuals exposed to therapeutic dose will develop idiosyncratic DILI that might involve severe clinical outcome, and no biomarker is available to identify the susceptible patients prior to drug treatment. In this editorial, we summarized the recent advances in predicting idiosyncratic DILI and provided the perspectives to improve the prediction.
药物性肝损伤(DILI)对制药行业、监管机构和临床医生来说是一项重大挑战。它通常分为“内在性”和“特异质性”,但大多数药物引起的DILI具有特异质性,通常无法从监管要求的动物毒性研究中预测出来。不幸的是,一些接受治疗剂量的个体可能会发生特异质性DILI,这可能会导致严重的临床后果,而且在药物治疗前没有生物标志物可用于识别易感患者。在这篇社论中,我们总结了预测特异质性DILI的最新进展,并提供了改进预测的观点。