Stephanie van Hoppe

64 Chapter 3 S U P P L EME N TA L MAT E R I A L SupplementalTable 1 - Pharmacokinetic parameters of osimertinib over 1.5 h after oral administration of 10 mg/kg osimertinib to male WT, Cyp3a -/- and Cyp3aXAV mice. Parameter Genotype Wild-type Cyp3a −/− Cyp3aXAV Plasma AUC 0-1.5 (h*ng/ml) 186 ± 14 94 ± 20*** 67 ± 19*** /# fold change 1 0.5 0.4 C max (ng/ml) 169 ± 2 74.7 ± 39.5 59.3 ± 45.4* T max (h) 1 1 0.5 - 1 C brain (ng/g) 723 ± 84 983 ± 283 942 ± 187 fold change 1 1.4 1.3 C liver (ng /g) 6755 ± 3068 4694 ± 2595 7886 ± 972 fold change 1 0.7 1.2 AUC, area under the plasma concentration-time curve; C max , maximumdrug concentration in plasma;T max , time (h) to reach maximum drug concentration in plasma; C tissue , tissue concentration; P tissue , tissue accumulation; ND, not determined. Statistical differences were assessed using one-way analysis of variance (ANOVA) followed by Tukey’s post-hoc multiple comparisons. *, P < 0.05; ***, P < 0.001 compared toWT mice, #, P < 0.05 compared to Cyp3a -/- mice. Data are expressed as the mean ± SD. (n = 5-6). Supplemental Figure 1 - Schematic representation of the metabolism of osimertinib to AZ5104 and AZ7550 by Cytochrome P450 (mainly CYP3A4). Supplemental Figure 1. Schematic representation of the metabolism of osimertinib to AZ5104 and AZ7550 by Cytochrome P450 (mainly CYP3A4).