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Cancer Res. 2010 Jan 15;70(2):440-6. doi: 10.1158/0008-5472.CAN-09-1947. Epub 2010 Jan 12.

Drug combination studies and their synergy quantification using the Chou-Talalay method.

Author information

1
Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. chout@mskcc.org

Abstract

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.

PMID:
20068163
DOI:
10.1158/0008-5472.CAN-09-1947
[Indexed for MEDLINE]
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