Chou Ting-Chao
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Pharmacol Rev. 2006 Sep;58(3):621-81. doi: 10.1124/pr.58.3.10.
The median-effect equation derived from the mass-action law principle at equilibrium-steady state via mathematical induction and deduction for different reaction sequences and mechanisms and different types of inhibition has been shown to be the unified theory for the Michaelis-Menten equation, Hill equation, Henderson-Hasselbalch equation, and Scatchard equation. It is shown that dose and effect are interchangeable via defined parameters. This general equation for the single drug effect has been extended to the multiple drug effect equation for n drugs. These equations provide the theoretical basis for the combination index (CI)-isobologram equation that allows quantitative determination of drug interactions, where CI < 1, = 1, and > 1 indicate synergism, additive effect, and antagonism, respectively. Based on these algorithms, computer software has been developed to allow automated simulation of synergism and antagonism at all dose or effect levels. It displays the dose-effect curve, median-effect plot, combination index plot, isobologram, dose-reduction index plot, and polygonogram for in vitro or in vivo studies. This theoretical development, experimental design, and computerized data analysis have facilitated dose-effect analysis for single drug evaluation or carcinogen and radiation risk assessment, as well as for drug or other entity combinations in a vast field of disciplines of biomedical sciences. In this review, selected examples of applications are given, and step-by-step examples of experimental designs and real data analysis are also illustrated. The merging of the mass-action law principle with mathematical induction-deduction has been proven to be a unique and effective scientific method for general theory development. The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.
通过对不同反应序列、机制及不同类型抑制作用进行数学归纳和推导，从平衡稳态下的质量作用定律原理得出的中位效应方程，已被证明是米氏方程、希尔方程、亨德森 - 哈塞尔巴尔赫方程和斯卡查德方程的统一理论。研究表明，通过定义的参数，剂量和效应是可互换的。这个单一药物效应的通用方程已扩展到n种药物的多药物效应方程。这些方程为组合指数（CI）-等效线图方程提供了理论基础，该方程可定量测定药物相互作用，其中CI < 1、= 1和> 1分别表示协同作用、相加作用和拮抗作用。基于这些算法，已开发出计算机软件，可在所有剂量或效应水平自动模拟协同作用和拮抗作用。它可显示体外或体内研究的剂量 - 效应曲线、中位效应图、组合指数图、等效线图、剂量降低指数图和多角图。这一理论发展、实验设计和计算机化数据分析有助于对单一药物评估或致癌物及辐射风险评估进行剂量 - 效应分析，也有助于生物医学科学众多学科领域中药物或其他实体组合的研究。在本综述中，给出了选定的应用实例，并说明了实验设计和实际数据分析的逐步示例。质量作用定律原理与数学归纳 - 推导的结合已被证明是通用理论发展的一种独特而有效的科学方法。中位效应原理及其基于质量作用定律的计算机软件在生物医学科学中的应用越来越广泛，从如何有效评估单一化合物或实体，到如何在联合治疗中有益地使用多种药物或治疗方式。
