Two isobolographic approaches in the evaluation of drug-drug interaction for non-parallel concentration-response curves in an in vitro study

Introduction and Objective.In in vitro cell line studies, two isobolographic analysis approaches are commonly used when assessing interactions between drugs.Both -the log-probit accompanied with Tallarida method and Chou-Talalay-Martin method -can distinguish pharmacodynamic types of interactions occurring between drugs.Materials and Method.The aim of the study is to assess the interaction between LY-2183240 and mitoxantrone in the malignant melanoma SK-MEL28 cell line in the MTT assay, by means of two methods -isobolographic (log-probit) accompanied by the Tallarida and Chou-Talalay-Martin method.Results.Log-probit accompanied by the Tallarida method revealed that LY-2183240 and mitoxantrone had non-parallel concentration-response curves, and produced an additive interaction in the SK-MEL28 cell line in the MTT assay.In contrast, the Chou-Talalay-Martin method showed that the combination of LY-2183240 and mitoxantrone exerted a synergistic interaction with a combination index value of 0.354.Conclusions.The observed discrepancy in the types of interactions between LY-2183240 and mitoxantrone in both methods resulted from the lack of assessment of mutual parallelism of the drugs concentrations-response curves in the Chou-Talalay-Martin method.The utmost caution is advised when utilizing the Chou-Talalay-Martin method in the detection of interactions in in vitro studies, especially for the combinations of drugs with non-parallel concentration-response curves.