Stephanie van Hoppe

121 Brain accumulation of ponatinib and its active metabolite is limited by ABCB1 and ABCG2 Supplementary Figure 3 - Brain and liver concentration ( A, D ), tissue-to-plasma ratio ( B, E ) and relative tissue accumulation ( C, F ) of DMP in female WT, Abcg2 -/- , Abcb1a/1b -/- , Abcg2;Abcb1a/1b -/- and Cyp3a -/- mice 24 h after oral administration of 10 mg/kg ponatinib. *, P < 0.05; **, P< 0.01; ***, P < 0.001 compared to WT mice. Data are given as mean ± SD. n = 4-5 mice per group. Su le entary Figure 3. Brain and liver concentration ( , ), tiss e-to-plasma ratio ( B, E ) and relative tissue accumulation ( C, F ) of DMP in female WT, Abcg2 -/- , Abcb1a/1b -/- , Abcg2;Abcb1a/1b -/- and Cyp3a - /- mice 24 h after oral administration of 10 mg/kg ponatinib. *, P < 0.05; **, P< 0.01; ***, P < 0.001 compared to WT mice. Data are given as mean ± SD. n = 4-5 mice per group. A B C D E F Brain concentration (ng/g) Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- Cyp3a-/- 0 100 200 300 400 500 *** 1.6-fold 57.8-fold 2.1-fold 1-fold ** Liver concentration (ng/g) Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- Cyp3a-/- 0 200 400 600 800 1000 *** *** 10-fold 0.8-fold 29-fold 1-fold Brain to plasma ratio Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- Cyp3a-/- 0 10 20 30 40 50 *** 4.3-fold *** 0.4-fold 1.2-fold 1-fold Liver to plasma ratio Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- Cyp3a-/- 0 20 40 60 80 100 * 1.8-fold 1-fold 2.1-fold 0.8-fold Brain accumulation (h -1 ) Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- Cyp3a-/- 0 0.25 0.5 0.75 1 *** 1.2-fold 15-fold 0.7-fold 1 -fold * Liver accumulation (h -1 ) Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- Cyp3a-/- 0.0 0.5 1.0 1.5 2.0 3.2-fold 0.9-fold 6.2-fold 0.7-fold *** *** 24 hours after oral administration