Zero interaction response surfaces for combined-action assessment.

Combined-action assessment requires first the calculation of combination effects expected for the case of no interaction. In a second step the experimental combination effects have to be compared to the expected ones in order to classify the combination as synergistic or antagonistic. Adopting the response surface methodology, a new procedure for the calculation of zero interaction response surfaces which can be applied both to various criteria for defining zero interaction and to various types of dose-response relations is proposed. The approach requires only information from single-agent dose-response relations, but provides nevertheless a comprehensive overview over the complete dose range under study. It can replace the tedious isobolographic analysis if the dose-additivity criterion is adopted.