药物导致肝损伤、药物处置及其代谢产物分析(英文)

Drug-induced liver injury,drug disposition and metabolite profiling

药物导致肝损伤是药物研发失败和上市药退市的一个主要原因。药物导致肝损伤的频发跟肝生理功能密切相关,因为大部分药物分子在体内的消除依赖于药物代谢或胆汁排泄的肝清除。虽然不少发病机制已有广泛的研究,但是大部分与药物导致肝损伤相关的机制仍然未明确。从这个意义上讲,代谢组学将成为研究药物导致肝损伤强有力的手段以有助于更好地了解其机制并进行相关生物标志物的鉴定。

Drug-induced liver injury （DILI） is a leading cause responsible for the failure of drug development and for the withdrawal of commercial drug products. The high frequency of DILl is due in part to the physiology of the liver, since in many cases elimination of drug molecules from the body is dependent on hepatic clearance via either metabolism or biliary excretion. Many of the mechanistic details underlying DILI remain poorly defined in spite of extensive studies of the pathogenesis. In this regard, metabolomies may become a powerful tool for investigation of DILI, leading to better mechanistic understanding and biomarkers identification.