Hamner-UNC Institute for Drug Safety Sciences, Research Triangle Park, North Carolina, USA.
Clin Pharmacol Ther. 2010 Sep;88(3):394-9. doi: 10.1038/clpt.2010.151. Epub 2010 Jul 28.
The occurrence of drug-induced liver injury (DILI) presents a significant safety issue for patients and represents a major cause of regulatory action. The methods that are in current use for early detection and prediction of DILI in patients are not adequate. The liver is the major site of synthesis of endogenous metabolites, and data suggest that alterations in the profiles of endogenous metabolites ("the metabolome") may precede development of clinically overt DILI. Metabonomics involves the application of analytical technologies such as nuclear magnetic resonance and mass spectrometry to detect changes in the metabolome. In this review, we describe the emerging role of metabonomics in predicting and understanding the mechanisms underlying DILI. Recent human clinical trials of drugs, including acetaminophen (APAP) and ximelagatran, have shown that the metabonomics of biofluids (plasma and urine) collected before and immediately after dosing can identify individual patients who are likely to develop DILI. These studies support the need to include metabonomic investigations in clinical trials of potentially hepatotoxic medications.
药物性肝损伤（DILI）的发生对患者的安全性构成了重大威胁，也是监管行动的主要原因。目前用于早期检测和预测患者 DILI 的方法并不充分。肝脏是内源性代谢物的主要合成部位，数据表明，内源性代谢物谱（“代谢组”）的改变可能先于临床明显 DILI 的发生。代谢组学涉及应用分析技术，如核磁共振和质谱，以检测代谢组的变化。在这篇综述中，我们描述了代谢组学在预测和理解 DILI 机制方面的新作用。最近对包括对乙酰氨基酚（APAP）和西米拉格兰在内的药物的人体临床试验表明，在给药前和给药后立即采集的生物流体（血浆和尿液）的代谢组学可以识别可能发生 DILI 的个体患者。这些研究支持在有潜在肝毒性的药物临床试验中纳入代谢组学研究的必要性。
