IMR Press / FBE / Volume 2 / Issue 2 / DOI: 10.2741/E116

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Emax model and interaction index for assessing drug interaction in combination studies

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1 Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Unit 1411, 1515 Holcombe Boulevard, Houston, Texas 77030, U.S.A.
2 Department of Bioinformatics and Biostatistics, School of Public Health and Information Sciences, University of Louisville, Louisville, Kentucky 40292, U.S.A.

*Author to whom correspondence should be addressed.

Academic Editor: William R. Greco

Front. Biosci. (Elite Ed) 2010, 2(2), 582–601; https://doi.org/10.2741/E116
Published: 1 January 2010
Abstract

Applying the Emax model in a Lowe additivity model context, we analyze data from a combination study of trimetrexate (TMQ) and AG2034 (AG) in media of low and high concentrations of folic acid (FA). The Emax model provides a sufficient fit to the data. TMQ is more potent than AG in both low and high FA media. At low TMQ:AG ratios, when a smaller amount of the more potent drug (TMQ) is added to a larger amount of the less potent drug (AG), synergy results. When the TMQ:AG ratio reaches 0.4 or larger in low FA medium, or when the TMQ:AG ratio reaches 1 or larger in high FA medium, synergy is weakened and drug interaction becomes additive. In general, synergistic effect in a dilution series is stronger at higher doses that produce stronger effects (closer to 1−Emax) than at lower dose levels that produce weaker effects (closer to 1). The two drugs are more potent in the low compared to the high FA medium. Drug synergy, however, is stronger in the high FA medium.

Keywords
additivity
antagonism
confidence interval estimation
Emax model
Loewe additivity model
nonlinear regression
synergy
trellis plot
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