Figure 2.
Graphical representation of the prediction model. A, The prediction distance (PD) for each metabolite is calculated at each concentration. These results are used to determine the composite prediction distance (CPD), which is the value used in the composite model. The area above and below the “Metabolite-Specific Cardiotoxic Response Thresholds” are associated with cardiotoxicity and the area between the “Metabolite-Specific Cardiotoxic Response Thresholds” are associated with noncardiotoxicity. B, The concentration-response curve for the composite model is illustrated with the black line. The concentration predicted by the point where the concentration-response curve of the composite model crosses the cardiotoxicity threshold (horizontal line) indicates the exposure level where a compound has the potential to cause cardiotoxicity (cardiotoxicity potential concentration, black bordered circle). For (A) and (B), the x-axis is the drug concentration. The y-axis is the solvent control-normalized (fold change) values for the metabolite response (A) or the composite prediction distance (B). C, Scoring algorithm employed for known cardiotoxicants (■) and noncardiotoxicants (●) utilizing the response at 10× Cmax (x-axis) to determine the performance of the composite model. The color image is available in the online version of this article.