Results of a virtual clinical trial elucidating tamoxifen dose escalation. Box-whisker-plots indicate the percentiles 5, 25, 50, 75, and 95 of the population simulation results. Shaded grey areas represent median and the percentiles 5 and 95 of simulated reference steady-state CYP2D6 EM levels (acc. to Figure 3) as target concentration ranges for all dose escalation regimens. Corresponding plasma concentrations after dose escalation of tamoxifen (20 mg twice daily over a period of 4 months) in breast cancer patients extracted by Irvin WJ, Jr. et al. (Irvin et al. 2011) are given as symbols. Abbreviations used in diagram: tamoxifen (TAM), N-desmethyltamoxifen (NDM), 4-hydroxytamoxifen (4OH), endoxifen (END), cytochrome P450 2D6 (CYP2D6), intermediate metabolizer (IM), poor metabolizer (PM).