Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method
Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method
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DOI：
10.1158/0008-5472.can-09-1947
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发表时间：
2010-01-15
期刊：
影响因子：
11.2
通讯作者：
Chou, Ting-Chao
中科院分区：
文献类型：
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作者：
Chou, Ting-Chao
这篇简短的观点文章集中在最常见的错误和陷阱，以及在药物组合研究中的做和不做，在实验设计，数据采集，数据解释和计算机模拟方面。用于药物组合的Chou-Talalay方法基于源自质量作用定律原理的中效方程，质量作用定律原理是提供单个实体与多个实体以及一阶和高阶动力学之间的共同联系的统一理论。这个通用方程包括生物化学和生物物理学中的Michaelis-Menten方程、Hill方程、Henderson-Hasselbalch方程和Scatchard方程。Chou-Talalay的组合指数（CI）定理为药物组合中的相加效应（CI = 1）、协同效应（CI < 1）和拮抗效应（CI > 1）提供了定量定义。该理论还提供了用于自动计算机模拟任何效应和剂量水平下的协同作用和/或拮抗作用的算法，分别如CI图和等值线图所示。Cancer Res; 70（2）; 440-6.（C）2010年AACR。
This brief perspective article focuses on the most common errors and pitfalls, as well as the do's and don'ts in drug combination studies, in terms of experimental design, data acquisition, data interpretation, and computerized simulation. The Chou-Talalay method for drug combination is based on the median-effect equation, derived from the mass-action law principle, which is the unified theory that provides the common link between single entity and multiple entities, and first order and higher order dynamics. This general equation encompasses the Michaelis-Menten, Hill, Henderson-Hasselbalch, and Scatchard equations in biochemistry and biophysics. The resulting combination index (CI) theorem of Chou-Talalay offers quantitative definition for additive effect (CI = 1), synergism (CI < 1), and antagonism (CI > 1) in drug combinations. This theory also provides algorithms for automated computer simulation for synergism and/or antagonism at any effect and dose level, as shown in the CI plot and isobologram, respectively. Cancer Res; 70(2); 440-6. (C)2010 AACR.