体外肝毒性评价细胞模型的研究进展

Progress of cell models for liver toxicity evaluation in vitro

药物性肝损伤是导致药物临床实验失败和上市后撤回的主要因素,而导致肝毒性药物进入临床实验的一个重要原因,是临床前动物模型与人类的种属差异。因此,开发新的临床前药物安全评价模型显得至关重要,临床前药物安全性评价模型中以人类肝细胞的体外培养为最可靠、快速、经济的模型。本文综述了在新药研发早期安全性评价中,不同体外模型的优点和不足之处,以期为药物安全性评价模型的进一步发展提供参考。

Drug-induced liver injury （DILI） is the primary cause of drug development failure during clini- cal trials and post-market withdrawal or warning issuing of approved drugs. The occurrence of DILI is attributable to the poor predictability of preclinical animal studies,which can be explained by several reasons, among which the most important one is the difference of drug metabolism between human and experimental species. Therefore, it is crucial to develop a new pre-clinical drug safety evaluation model. Among the current models, human hepatocytes models are not only less time- and money-consuming but also reliable for predicting hepatotoxicity. This review de- scribes the advantages and limitations of hepatic cell-based in vitro models for early safety risk assessment during drug development with the hope to provide reference to further development of drug safety evaluation model.