Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130, USA.
Curr Drug Metab. 2010 May;11(4):369-78. doi: 10.2174/138920010791514261.
Using graphic rules to deal with kinetic systems is an elegant approach by combining the graph representation (schematic representation) and rigorous mathematical derivation. It bears the following advantages: (1) providing an intuitive picture or illuminative insights; (2) helping grasp the key points from complicated details; (3) greatly simplifying many tedious, laborious, and error-prone calculations; and (4) able to double-check the final results. In this mini review, the non-steady state graphic rule in enzyme-catalyzed kinetics and protein-folding kinetics was extended to cover drug-metabolic systems. As a demonstration, a step-by-step illustration is presented showing how to use the graphic rule to derive the concentrations of the parent drug and its metabolites vs. time for the seliciclib, vildagliptin, and cyclin-dependent kinase inhibitor (AG-024322) metabolic systems, respectively. It can be seen from these paradigms that the graphic rule is particularly useful to analyze complicated drug metabolic systems and ensure the correctness of the derived results. Meanwhile, the intuitive feature of graphic representation may facilitate analyzing and classifying drug metabolic systems; e.g., according to their directed graphs, the metabolism of seliciclib and the metabolism of vildagliptin can be categorized as 0-->5 mechanism while that of AG-024322 as 0-->4-->3 mechanism.
运用图形规则来处理动力学系统是一种巧妙的方法，它结合了图形表示（示意图表示）和严格的数学推导。它具有以下优点：（1）提供直观的图像或有启发性的见解；（2）帮助从复杂的细节中抓住要点；（3）大大简化了许多繁琐、费力且容易出错的计算；（4）能够对最终结果进行双重检查。在这篇迷你综述中，将酶催化动力学和蛋白质折叠动力学中的非稳态图形规则扩展到涵盖药物代谢系统。作为一个范例，逐步展示了如何使用图形规则推导出塞利昔布、维格列汀和细胞周期蛋白依赖性激酶抑制剂（AG-024322）代谢系统中母体药物及其代谢物随时间的浓度变化。从这些范例中可以看出，图形规则对于分析复杂的药物代谢系统和确保推导结果的正确性特别有用。同时，图形表示的直观特征可能有助于分析和分类药物代谢系统；例如，根据它们的有向图，塞利昔布的代谢和维格列汀的代谢可以归类为 0-->5 机制，而 AG-024322 的代谢归类为 0-->4-->3 机制。
