Stephanie van Hoppe

66 Chapter 3 Supplemental Figure 3. Tissue concentration ( A, C, E & G ) and tissue accumulation ( B, D, F & H ) of osimertinib at 24 h in male WT, Abcb1a/1b;Abcg2 -/- , and Cyp3a -/- mice following a single oral dose of 10 mg/kg osimertinib. Statistical differences were assessed using one-way analysis of variance WT Abcb1a/1b -/- ; Abcg2 -/- Cyp3a -/- 0 1 2 3 100 200 300 400 Brain concentration of osimertinib (ng/g) <LLoQ WT Abcb1a/1b -/- ; Abcg2 -/- Cyp3a -/- 0 50 100 150 200 250 Kidney concentration of osimertinib (ng/g) WT Abcb1a/1b -/- ; Abcg2 -/- Cyp3a -/- 0 100 200 300 Liver concentration of osimertinib (ng/g) *** WT Abcb1a/1b -/- ; Abcg2 -/- Cyp3a -/- 0 50 100 150 200 250 Spleen concentration of osimertinib (ng/g) * WT Abcb1a/1b -/- ; Abcg2 -/- Cyp3a -/- 0 50 100 150 Brain accumulation of osimertinib (*10 -3 h -1 ) <LLoQ 24 hours experiment WT Abcb1a/1b -/- ; Abcg2 -/- Cyp3a -/- 0 10 20 30 40 50 Spleen accumulation of osimertinib (*10 -3 h -1 ) A B C E G D F H WT Abcb1a/1b -/- ; Abcg2 -/- Cyp3a -/- 0 50 100 150 Liver accumulation of osimertinib (*10 -3 h -1 ) *** WT Abcb1a/1b -/- ; Abcg2 -/- Cyp3a -/- 0 20 40 60 Kidney accumulation of osimertinib (*10 -3 h -1 )