Modeling synergistic and antagonistic interactions in xenobiotic compounds.

Abstract

Over time, synergistic/antagonistic interactions between pairs of compounds has been examined from a variety of viewpoints that impose difficulties in comparative studies. The increasing importance of potentiated activity in plant–organism interfaces mediated by secondary phytometabolites and also of inter- and intraspecific animal interactions, and their ecological impact in terms of increased cost effectiveness and organism fittness in the production of active compounds, demands that a standard methodology be designed to ascertain the amount of synergism/antagonism of A + [B, C, ..., Z] mixtures. Here we preface one such method, based on the comparison of theoretically predicted addition of dose–response (D/R) curves of pairs of compounds mixed in 0–100% relative proportions and constant added dosage, examined at various total dosages, with experimental results of similarly composed mixtures. It is shown that large effects in the activity prediction curves occur as a consequence of minor changes in the D/R profiles of individual compounds. These changes may lead to equivocal assessment of potentiation by application of coactivity coefficients without close examination of predicted curves. Evaluation of this method with literature from the data surveyed illustrated its potentially general application in studies of compound synergism.