Fig. 5.

Correlation of predicted and observed drug–drug interaction (DDI) area under the plasma concentration–time curve (AUC) ratios and DDI maximum plasma concentration (C_max) ratios of all studies. The upper panel illustrates DDI AUC ratios (a) and DDI C_max ratios (b) of the gemfibrozil–repaglinide, itraconazole–repaglinide, gemfibrozil–itraconazole–repaglinide, rifampicin–repaglinide, or clarithromycin–repaglinide DDIs. The lower panel illustrates DDI AUC ratios (c) and DDI C_max ratios (d) of the gemfibrozil–pioglitazone, itraconazole–pioglitazone, gemfibrozil–itraconazole–pioglitazone, or rifampicin–pioglitazone DDIs. The colors represent different perpetrator drugs and the symbols the victim drugs repaglinide (dots) and pioglitazone (triangles). The straight black line marks the line of identity. Light grey lines indicate 0.8- to 1.25-fold and dark grey lines indicate 0.5- to 2-fold acceptance limits. The curved black lines show the prediction success limits suggested by Guest et al. [41]. Detailed information about dosing regimens and study populations is given in Electronic Supplementary Material (ESM) Tables S4.2.1, S4.3.1, S4.4.1, S4.5.1, S4.6.1, S4.7.1, S4.8.1, S4.9.1, and S4.10.1. The plotted DDI AUC ratios and C_max ratios are listed in ESM Tables S4.2.2, S4.3.2, S4.4.2, S4.5.2, S4.6.2, S4.7.2, S4.8.2, S4.9.2, and S4.10.2