PMID: 6382953Jan 1, 1984Paper

Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors

Advances in Enzyme Regulation
T C Chou, P Talalay

Abstract

A generalized method for analyzing the effects of multiple drugs and for determining summation, synergism and antagonism has been proposed. The derived, generalized equations are based on kinetic principles. The method is relatively simple and is not limited by whether the dose-effect relationships are hyperbolic or sigmoidal, whether the effects of the drugs are mutually exclusive or nonexclusive, whether the ligand interactions are competitive, noncompetitive or uncompetitive, whether the drugs are agonists or antagonists, or the number of drugs involved. The equations for the two most widely used methods for analyzing synergism, antagonism and summation of effects of multiple drugs, the isobologram and fractional product concepts, have been derived and been shown to have limitations in their applications. These two methods cannot be used indiscriminately. The equations underlying these two methods can be derived from a more generalized equation previously developed by us (59). It can be shown that the isobologram is valid only for drugs whose effects are mutually exclusive, whereas the fractional product method is valid only for mutually nonexclusive drugs which have hyperbolic dose-effect curves. Furthermore, in the isobol ...Continue Reading

References

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Citations

May 1, 1997·Journal of Clinical Pharmacology·J J Zimmerman, B D Kahan
Jan 1, 1996·Transplant International : Official Journal of the European Society for Organ Transplantation·B D Kahan
Jan 1, 1992·Cancer Chemotherapy and Pharmacology·R P PerezT C Hamilton
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Aug 21, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Linhua JinMarina Konopleva
Feb 26, 2005·Cancer Chemotherapy and Pharmacology·Risa TanakaShuji Nakano
May 6, 2005·Cancer Chemotherapy and Pharmacology·Risa TanakaShuji Nakano
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Nov 18, 2005·Cancer Chemotherapy and Pharmacology·Terzah M HortonStacey L Berg
Mar 3, 2007·Cancer Chemotherapy and Pharmacology·Julie ScottTerry H Landowski

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