Fig. 5.

Impact of drug–drug interaction (DDI) and drug–drug–gene interaction (DDGI). Population predictions of metformin plasma concentration–time profiles before and during cimetidine co-treatment of different SLC22A2 genotypes, compared to observed data [21, 23, 33]. Population prediction arithmetic means are shown as solid blue (metformin only) or dashed red (DDI or DDGI) lines; the shaded areas illustrate the respective 68% population prediction intervals. Observed data are shown as dots (metformin only) or triangles (DDI or DDGI) ± standard deviation. Details on the study protocols, semilogarithmic plots, and quantitative DDI and DDGI prediction performance measures are provided in the ESM. bid twice daily, GG SLC22A2 808GG genotype, GT SLC22A2 808GT genotype, po oral, qd once daily, qid four times daily, TT SLC22A2 808TT genotype