AZD1775 MS Supplementary Materials from Quantitative and Mechanistic Understanding of AZD1775 Penetration across Human Blood–Brain Barrier in Glioblastoma Patients Using an IVIVE–PBPK Modeling Approach

SUPPLEMENTARY METHODS Supplementary Figure 1 Overall metabolic kinetics of AZD1775 in human liver and intestinal microsomes (HLM and HIM). Supplementary Figure 2 PBPK model simulations showing the impact of BBB integrity (i.e., PSB), transporter activity (i.e., CLefflux,vivo and CLuptake,vivo), and drug binding to brain tissues (i.e., fu,br) on the extent of AZD1775 BBB penetration (assessed by Kp,uu) and the rate of penetration (assessed by Tmax,br).