Calculating slope and ED50 of additive dose-response curves, and application of these tabulated parameter values.

Comparing dose-response curves (DRCs) of a compound A in the absence and presence of a fixed dose of an antagonist B is standard in pharmacology and toxicology. When B qualitatively resembles A in its action, it is often useful to construct theoretical DRCs of additive and independent combinations. Theoretical curves are calculated from experimental values by the program ALLFIT, which uses the four parameter logistic equation. DRCs of theoretical, additive DRCs are obtained by using the respective values for slope and ED50, which were taken from tables presented here compiled on the basis of the slope of the DRC of A alone (0.6-14) and of the effect of B alone (1-75%). These tables are unnecessary for the construction of theoretical curves if A acts by an independent mechanism, giving values for slope and ED50 identical to those of the DRC of A alone. Experimental DRCs of antiviral and other effects (the latter taken from data in the literature) are compared with theoretical curves by an F-test analysis provided by ALLFIT. The method can be used successfully for the construction of theoretical curves for additive and independent DRCs and comparison with experimental curves. This comparison may help clarify the mode of interaction of A with B.