The following paper and site may be interested, plz check out.

Best wishes

http://clincancerres.aacrjournals.org/content/21/20/4686.figures-only

Article Radiosensitization with combined use of olaparib and PI-103 ...

For drug combination index, I used Compusyn. For ratio, I just used 0.25x, 0.5x and 1x IC50 of each drug/compound.

Thanks all

I', interest the compusync program. Is it free?  

Yes. The compusyn programme is free. You just need to register and install. However my major complaint is you have to key in manually the data. I do not think we can import excel file. There are various paper and also tutorial video.

Hi Reagan,

I have an another one question. Assume that LC50 of drug A is 20 ug/ml and   LC50 of drug B is 100 ug/ml. So, the 1:1 of LC50 mean 20 ug/ml of drug A + 100 ug/ml of drug B

; 1:1 0.5x LC50 mean 10ug/ml of drug A + 50 ug/ml of drug B. Right???  Can you explain me?

Best thanks

Yes Sarit. That's correct. However you do have to keep in mind that using 0.5x, 1x combination is just another screening process. Some drug might have synergistic at different concentration ratio, ie 0.25LC50 drug A combine with 1.0LC50 drug B might have synergistic higher than ratio 1:1. Best to do a lot more ratios if you really want to determine the best ratio once you identified best drug combination. And also you might have to do pretreatment, to see if drug A or drug B that enhanced the activity. Glad I can help you with this. I myself just finished with the pretreatment assay.

Wow!!

Thanks a lot for your question. Hope your best rusults in your works. 

Dear colleagues Sarit,

Synergism and its effect as a basic rule of thumb is when they amplified in their effect, as they belong to the same group of drugs!

  In my clinical experience every synergist when administered in combination may be reduced to a dose of from 1/3 to 1/2 less than its Referential doses, and to give a better therapeutic effect is cumulative, and reduces the side effects of the drug when administered in monotherapy!

regards

 Dear colleagues Sarit,

I forgot one important thing to note on that particular attention should be paid: that there are cases in clinical pharmacology fact rarely or there that is common synergist effect is greater than the sum of their individual effects of this type supraditivnog synergism is very difficult to reliably in two synergistic drug .

Best wishes

Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method

Ting-Chao Chou

DOI: 10.1158/0008-5472.CAN-09-1947 Published January 2010

Article

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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. Cancer Res; 70(2); 440–6

Introduction

http://cancerres.aacrjournals.org/content/70/2/440

Giving a simple example, if the untreated is 100%, drug A (1uM) reduces the cell number to 60%, drug B (1 uM) is 60%, drug A (1uM) plus B (1uM) together is also 60%, I think this is the antagonizing effect of these two drugs, is that right?

I am not sure but it would have been antagonism since there were no added value. Usually you would use lower concentration in combination vs high concentration as single agent as mentioned by Jasenko. And also the slope of cytotoxicity graph for each drug can differ from each other although they might share 1 single point which would also affect the type of interaction. But there are things need to be considered is the potential of synergistic or compounded side effects. It is always good to have a normal cell control although some might argue immortalized "normal" cell lines are not real "normal". For screening purpose, the combination index from CompuSyn will allow you to choose a good combination candidate against multiple cell lines. This is just my thought, probably there are other more experience researchers can help you further.

Hey guys, I'm facing the following problem at the moment: when doing simple toxicity tests, I find that the combination of a certain compound with (in this case) cisplatin shows enhanced sensitivy of my before resistant cells...but in my combination index studies the results tell me, that the combination has antagonistic effects and I'm totally baffled by that... Did anyone of you face this problem as well? Could there be any saturation effects that the Chou equation did not consider?

I treated my cells with 0,1 - 0,2 - 0,4 - 0,6 - 0,8 - 1 - 2 - 4 - 8 of the EC50, for wildtype and resistant cells separately and used CompuSyn for the calculation.

Thanks in advance!

Check the attached articles for more information.