Analysis of combined drug effects: a new look at a very old problem

A simple, general and novel method for the quantitative analysis of combined drug effects is presented. The procedure determines if the drug combinations are additive, synergistic or antagonistic, regardless of whether the dose-effect curves are hyperbolic (first order) or sigmoidal (higher order), or whether the effects of the drugs are totally independent or not. We believe that the proposed method (median-effect plot) suffers from fewer restrictions and is more widely applicable than the isobologram or the fractional product method. It provides insight into the nature of the dose-effect relationship with relatively few measurements. We illustrate the procedure by analysing the combined lethal effects of two insecticides on house-flies.