Hepatology Research Group, Department of Clinical Research, Faculty of Medicine, University of Bern, Murtenstrasse 35, 3010 Bern, Switzerland.
Biochem Pharmacol. 2013 Jan 1;85(1):12-20. doi: 10.1016/j.bcp.2012.08.013. Epub 2012 Aug 23.
Metabolomics is the global and unbiased survey of the complement of small molecules (say, <1 kDa) in a biofluid, tissue, organ or organism and measures the end-products of the cellular metabolism of both endogenous and exogenous substrates. Many drug candidates fail during Phase II and III clinical trials at an enormous cost to the pharmaceutical industry in terms of both time lost and of financial resources. The constantly evolving model of drug development now dictates that biomarkers should be employed in preclinical development for the early detection of likely-to-fail candidates. Biomarkers may also be useful in the preselection of patients and through the subclassification of diseases in clinical drug development. Here we show with examples how metabolomics can assist in the preclinical development phases of discovery, pharmacology, toxicology, and ADME. Although not yet established as a clinical trial patient prescreening procedure, metabolomics shows considerable promise in this regard. We can be certain that metabolomics will join genomics and transcriptomics in lubricating the wheels of clinical drug development in the near future.
代谢组学是对生物体液、组织、器官或生物体中小分子（<1 kDa）的整体和无偏检测，测量内源性和外源性底物细胞代谢的终产物。许多候选药物在 II 期和 III 期临床试验中失败，这给制药行业带来了巨大的时间和财务资源损失。药物开发的不断发展的模式现在要求在临床前开发中使用生物标志物来早期检测可能失败的候选药物。生物标志物也可用于临床药物开发中的患者初步选择和疾病的细分。在这里，我们通过示例展示了代谢组学如何在发现、药理学、毒理学和 ADME 的临床前开发阶段提供帮助。尽管代谢组学尚未确立为临床试验患者的预筛选程序，但在这方面显示出了相当大的前景。我们可以肯定的是，代谢组学将在不久的将来与基因组学和转录组学一起为临床药物开发的顺利进行提供支持。
