Stephanie van Hoppe

41 ABCG2 & ABCB1 transport afatinib and restrict its oral availability and brain accumulation Supplementary Figure 6 - 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 2 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 -/- mice. Data are given as mean ± SD. Supplementary Figure 6 : 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 2 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 -/- mice. Data are given as mean ± SD. *** *** *** *** ++ ++ *** *** ** WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0 10 20 30 Kidney concentration (µg/g) WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0 50 100 150 200 Kindey toplasma ratio WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0 50 100 150 Kidney accumulation (hr -1 ) WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0 10 20 30 40 Spleenconcentration (µg/g) WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0 50 100 150 200 Spleen toplasma ratio WT Abcg2-/- Abcb1a/1b-/- Abcg2;Abcb1a/1b-/- 0 50 100 150 Spleenaccumulation (hr -1 ) A B D C F E 2-hour experiment

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