A reliable translation of in vitro and preclinical data on drug absorption, distribution, metabolism, and excretion (ADME) to humans is important for safe and effective drug development. Precision medicine that is expected to provide the right clinical dose for the right patient at the right time requires a comprehensive understanding of population factors affecting drug disposition and response. Characterization of drug-metabolizing enzymes and transporters for the protein abundance and their interindividual as well as differential tissue and cross-species variabilities is important for translational ADME and precision medicine. This review first provides a brief overview of quantitative proteomics principles including liquid chromatography–tandem mass spectrometry tools, data acquisition approaches, proteomics sample preparation techniques, and quality controls for ensuring rigor and reproducibility in protein quantification data. Then, potential applications of quantitative proteomics in the translation of in vitro and preclinical data as well as prediction of interindividual variability are discussed in detail with tabulated examples. The applications of quantitative proteomics data in physiologically based pharmacokinetic modeling for ADME prediction are discussed with representative case examples. Finally, various considerations for reliable quantitative proteomics analysis for translational ADME and precision medicine and the future directions are discussed.

中文翻译：

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转化吸收、分布、代谢、排泄和精准医学中的定量蛋白质组学

将药物吸收、分布、代谢和排泄 (ADME) 的体外和临床前数据可靠地转化为人类对于安全有效的药物开发非常重要。精准医疗期望在正确的时间为正确的患者提供正确的临床剂量，需要全面了解影响药物处置和反应的人群因素。药物代谢酶和转运蛋白的蛋白质丰度及其个体间以及差异组织和跨物种变异性的表征对于转化 ADME 和精准医学非常重要。本综述首先简要概述了定量蛋白质组学原理，包括液相色谱-串联质谱工具、数据采集方法、蛋白质组学样品制备技术、和质量控制，以确保蛋白质定量数据的严谨性和可重复性。然后，通过表格示例详细讨论了定量蛋白质组学在体外和临床前数据翻译以及个体间变异预测中的潜在应用。通过代表性案例讨论了定量蛋白质组学数据在 ADME 预测的基于生理学的药代动力学模型中的应用。最后，讨论了转化 ADME 和精准医学的可靠定量蛋白质组学分析的各种考虑因素以及未来的方向。通过表格示例详细讨论了定量蛋白质组学在体外和临床前数据转化以及预测个体差异方面的潜在应用。通过代表性案例讨论了定量蛋白质组学数据在 ADME 预测的基于生理学的药代动力学模型中的应用。最后，讨论了转化 ADME 和精准医学的可靠定量蛋白质组学分析的各种考虑因素以及未来的方向。通过表格示例详细讨论了定量蛋白质组学在体外和临床前数据转化以及预测个体差异方面的潜在应用。通过代表性案例讨论了定量蛋白质组学数据在 ADME 预测的基于生理学的药代动力学模型中的应用。最后，讨论了转化 ADME 和精准医学的可靠定量蛋白质组学分析的各种考虑因素以及未来的方向。