Stephanie van Hoppe

50 Chapter 3 Figure 1 - In vitro transport of osimertinib. Transepithelial transport of osimertinib (2 μM) was assessed in MDCK-II cells either non-transduced ( A, B ) or transduced with hABCB1 ( C, D ), hABCG2 ( E, F ), or mAbcg2 ( G, H ) cDNA. At t = 0 h osimertinib was added to the donor compartment; thereafter at t = 1, 2, 4 and 8 h osimertinib concentrations were measured and plotted as total amount (pmol) of translocated drug (n = 3). ( B, D−H ) Zosuquidar (5 μM) and/or Ko143 (5 μM) were added as indicated to inhibit hABCB1 or hABCG2 and mAbcg2, respectively. r, relative transport ratio at 8 h. BA (red triangles), translocation from the basolateral to the apical compartment; AB (black circles), translocation from the apical to the basolateral compartment. Data are presented as mean ± SD. Figure 1. In vitro transport of osimertinib. Transepithelial transport of osimertinib (2 μM) was assessed in MDCK-II c lls either no -transduced ( A, B ) or transduced with hABCB1 ( C, D ), hABCG2 ( E, F ), or mAbcg2 ( G, H ) cDNA. At t = 0 h osimertinib was ad ed to t e donor compartment; thereafter at t = 1, 2, 4 and 8 h osimertinib conc n rations were measured an pl tted as total amount (pmol) of translocated drug (n = 3). ( B, D−H ) Zosuquidar (5 μM) and/or Ko143 (5 μM) were added as indic ted to inhibit hABCB1 or hABCG2 and mAbcg2, espectively. r, elative transport ratio at 8 h. BA (red triangles), translocation from the basolateral to the ap cal compartment; AB (black circles), t ansloc tion from the apical to the basolateral comp r ment. Data re presen ed as mean ± SD. Parental 0 2 4 6 8 0 30 60 90 120 150 180 Time (h) Osimertinib transport (pmol) AB BA r = 1.0 A Parental + Zosuquidar Time (h) Osimertinib transport (pmol) 0 2 4 6 8 0 30 60 90 120 150 180 AB BA r = 0.8 B hABCB1 Time (h) Osimertinib transport (pmol) 0 2 4 6 8 0 30 60 90 120 150 180 r = 1.7 C hABCB1 + Zosuquidar Time (h) Osimertinib transport (pmol) 0 2 4 6 8 0 30 60 90 120 150 180 r = 1.1 D hABCG2 + Zosuquidar Time (h) Osimertinib transport (pmol) 0 2 4 6 8 0 30 60 90 120 150 180 r = 0.9 E hABCG2 + Zosuquidar + Ko143 Time (h) Osimertinib transport (pmol) 0 2 4 6 8 0 30 60 90 120 150 180 r = 0.7 F mAbcg2 + Zosuquidar 0 2 4 6 8 0 30 60 90 120 150 180 Time (h) Osimertinib transport (pmol) r = 2.3 G mAbcg2 + Zosuquidar + Ko143 Time (h) Osimertinib transport (pmol) 0 2 4 6 8 0 30 60 90 120 150 180 r = 1.2 H