Stephanie van Hoppe

40 Chapter 2 Supplementary Figure 5 - Kidney and spleen concentration (A, D), tissue-to-plasma ratio (B, E) and relative accumulation (C, F) of afatinib in femaleWT, Abcg2 -/- , Abcb1a/1b -/- and Abcg2;Abcb1a/1b -/- mice 24 h after oral administration of 10 mg/kg afatinib. *, P < 0.05; **, P < 0.01; ***, P <0.001 compared to WT mice; +, P < 0.05, ++, P < 0.01, +++, P < 0.001 compared to Abcg2;Abcb1a/1b -/- and ### P < 0.001. Data are given as mean ± SD. Supplementary Figure 5 : Kidney and spleen concentration ( A, D ), tissue-to-plasma ratio ( B, E ) and relative accumulation ( C, F ) of afatinib in female WT, Abcg2 -/- , Abcb1a/1b -/- and Abcg2;Abcb1a/1b -/- mice 24 h after oral administration of 10 mg/kg afatinib. *, P < 0.05; **, P < 0.01; ***, P <0.001 compared to WT mice; + , P < 0.05, ++ , P < 0.01, +++ , P < 0.001 compared to Abcg2;Abcb1a/1b -/- and ### P < 0.001. Data are given as mean ± SD. *** +++ +++ *** +++ +++ ++ WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0 2 4 6 8 Kidney concentration (µg/g) *** +++ +++ WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0 200 400 600 800 Kidney toplasma ratio N.D. (<LLOQ) +++ ### WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0.0 0.5 1.0 1.5 2.0 2.5 Kidney accumulation (hr -1 ) *** +++ +++ WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0 2 4 6 8 10 Spleenconcentration (µg/g) WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0 200 400 600 Spleen toplasma ratio N.D. (<LLOQ) WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0 1 2 3 Spleenaccumulation (hr -1 ) A B D C F E 24-hour experiment

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