Stephanie van Hoppe

95 ABCB1 restricts brain penetration of the BTK inhibitor ibrutinib while CYP3A limits its oral bioavailability Supplemental Figure 6 - Kidney and spleen concentration ( A, D ), tissue-to-plasma ratio ( B, E ) and relative tissue accumulation ( C, F ) of ibrutinib-DiOH (DiOH) in female WT, Abcb1a/1b -/- , Abcg2 -/- and Abcb1a/1b;Abcg2 -/- mice 1 h after oral administration of 10 mg/kg ibrutinib. *, P < 0.05; **, P < 0.01; ***, P < 0.001 compared toWT mice. Data are given as mean ± SD. n = 5−6 mice per group. Supplemental Figure 7 - Ibrutinib-DiOH (DiOH) to ibrutinib concentration ratio in plasma of female WT (black circles), Cyp3a -/- (blue squares) and Cyp3aXAV (purple triangles) mice over 3 h after oral administration of 10 mg/kg ibrutinib. Data are given as mean ± SD. n = 5−6 mice per group. Supplemental Figure 6. Kidney and spleen concentration ( A, D ), tissue-to-plasma ratio ( B, E ) and relative tissue accumulation ( C, F ) of ibrutinib-DiOH (DiOH) in female WT, Abcb1a/1b -/- , Abcg2 -/- and Abcb1a/1b;Abcg2 -/- mice 1 h after oral administration of 10 mg/kg ibrutinib. *, P < 0.05; **, P < 0.01; ***, P < 0.001 compared to WT mice. Data are given as mean ± SD. n = 5−6 mice per group. WT Abcg2 -/- Abcb1a/1b -/- Abcb1a/1b;Abcg2 -/- 0 200 400 600 800 1000 DiOH kidneys concentration (ng/g) WT Abcg2 -/- Abcb1a/1b -/- Abcb1a/1b;Abcg2 -/- 0 100 200 300 400 500 DiOH spleen concentration( ng/g) WT Abcg2 -/- Abcb1a/1b -/- Abcb1a/1b;Abcg2 -/- 0.0 0.5 1.0 1.5 2.0 DiOH Kidney to plasma ratio WT Abcg2 -/- Abcb1a/1b -/- Abcb1a/1b;Abcg2 -/- 0.0 0.2 0.4 0.6 0.8 DiOH spleen accumulation (h -1 ) A B C D E F 1-hour experiment WT Abcg2 -/- Abcb1a/1b -/- Abcb1a/1b;Abcg2 -/- 0.0 0.2 0.4 0.6 0.8 DiOH spleen to plasma ratio -1 WT Abcg2 -/- Abcb1a/1b -/- Abcb1a/1b;Abcg2 -/- 0.0 0.5 1.0 1.5 DiOH kidney accumulation (h )