Stephanie van Hoppe

122 Chapter 5 Supplementary Figure 4 - 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 -/- and Abcg2;Abcb1a/1b -/- mice 2 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 = 3-5 mice per group. Supplementary Figure 4. 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 -/- and Abcg2;Abcb1a/1b -/- mice 2 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 = 3-5 mice per group. A B C D E F Brain concentration (ng/g) Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- 0 20 40 60 80 100 7.6-fold *** 0.7-fold 0.4-fold * Liver concentration (ng/g) Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- 0 1000 2000 3000 4000 ** *** 1.5-fold 0.3-fold 0.6-fold Brain to plasma ratio Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- 0 1 2 3 ** 4.5-fold 0.5-fold *** Liver to plasma ratio Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- 0 50 100 150 200 * 0.6-fold ** 0.6-fold Brain accumulation (h -1 ) Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- 0.0 0.5 1.0 1.5 2.0 *** 3.9-fold 0.6-fold 0.7-fold Liver accumulation (h -1 ) Wild-type Abcg2-/- Abcb1a/1b-/- Abcb1a/1b;Abcg2-/- 0 50 100 150 0.9-fold 0.4-fold ** ** 0.8-fold 2 hours after oral administration