Stephanie van Hoppe

39 ABCG2 & ABCB1 transport afatinib and restrict its oral availability and brain accumulation Supplementary Figure 3 - Kidney and spleen concentration (A, D), tissue-to-plasma ratio (B, E) and relative accumulation (C, F) of afatinib in female WT and Abcg2;Abcb1a/1b -/- mice 8 h after oral administration of 10 mg/kg afatinib. Data are given as mean ± SD. Supplementary Figure 4 - Plasma concentration-time curves of afatinib in female WT (black squares), Abcg2 -/- (blue triangles), Abcb1a/1b -/- (green triangles), and Abcg2;Abcb1a/1b -/- (red squares) over 24 hours after oral administration of 10 mg/kg afatinib. Data are given as mean ± SD and shown in a semi-log plot to illustrate clearance differences at 4-8 h. Note that the WT 24-h time point shows a maximum estimate of the plasma concentration, given that this value was below the quantification limit. The actual concentration may therefore well have been considerably lower (dotted arrow), for this reason this part of the graph is depicted as a dotted line. Supplementary Figure 3 : Kidney and spleen concentration ( A, D ), tissue-to-plasma ratio ( B, E ) and relative accumulation ( C, F ) of afatinib in female WT and Abcg2;Abcb1a/1b -/- mice 8 h after oral administration of 10 mg/kg afatinib. Data are given as mean ± SD. WT Abcg2;Abcb1a/1b-/- 0 5000 10000 15000 20000 Kidney concentration (ng/g) WT Abcg2;Abcb1a/1b-/- 0 10000 20000 30000 40000 50000 Spleenconcentration (ng/g) WT Abcg2;Abcb1a/1b-/- 0 100 200 300 400 kidney toplasma ratio WT Abcg2;Abcb1a/1b-/- 0 200 400 600 Spleen toplasma ratio WT Abcg2;Abcb1a/1b-/- 0 5 10 15 Kidney accumulation (hr -1 ) WT Abcg2;Abcb1a/1b-/- 0 5 10 15 20 25 Spleenaccumulation (hr -1 ) A B D C F E 8-hour experiment Supplementary Figure 4 : Plasma concentration-time curves of afatinib in female WT (black squares), Abcg2 -/- (blue triangles), Abcb1a/1b -/- (green triangles), and Abcg2;Abcb1a/1b -/- (red squares) over 24 hours after oral administration of 10 m /kg afatinib. Data are given as mean ± SD and shown in a semi- log plot to illustrate clea nce dif erences at 4-8 h. Note th t th WT 24-h time point shows a maximum estimate of the plasma co centration, given that this value was below the quantification limit. The actual concentration may therefore well have been considerably lower (dotted arrow), for this reason this part of the graph is depicted as a dotted line.