Stephanie van Hoppe

106 Chapter 5 Figure 1 . In vitro transport of ponatinib. Transepithelial transport of ponatinib (5 µM) was assessed in MDCK-II cells either non-transduced ( A, B ) or transduced with hABCB1 ( C, D ), mAbcg2 ( E, F ), or hABCG2 ( G, H ) cDNA. At t = 0 h ponatinib was added to the donor compartment; thereafter at t = 4 and 8 h the concentrations were measured and plotted as total amount (ng) of transport (n = 3). B, D- H : Zosuquidar (5 µM) or Ko143 (5 µM) were added as indicated to inhibit hABCB1 or hABCG2 and mAbcg2, respectively. r, relative transport ratio. BA (red squares, dashed line) translocation from the basolateral to the apical compartment; AB (blue circles), translocation from the apical to the parental Time (h) 2 4 6 8 0 50 100 150 Transport (ng) r = 0.8 parental + zosuquidar Time (h) Transport (ng) 2 4 6 8 0 50 100 150 AB BA r = 1.0 hABCB1 Time (h) Transport (ng) 2 4 6 8 0 50 100 150 r = 1.8 hABCB1 + zosuquidar Time (h) Transport (ng) 2 4 6 8 0 50 100 150 AB BA r = 0.9 mAbcg2 + zosuquidar Time (h) Transport (ng) 2 4 6 8 0 50 100 150 r = 2.3 mAbcg2 + zosuquidar + Ko143 Time (h) Transport (ng) 2 4 6 8 0 50 100 150 AB BA r = 1.3 hABCG2 + zosuquidar Time (h) Transport (ng) 2 4 6 8 0 50 100 150 r = 0.9 hABCG2 + zosuquidar + Ko143 Time (h) Transport (ng) 2 4 6 8 0 50 100 150 AB BA r = 1.0 A B C E G D F H Figure 1 - In vitro transport of ponatinib. Transepithelial transport of ponatinib (5 µM) was assessed in MDCK-II cells either non-transduced ( A, B ) or transduced with hABCB1 ( C, D ), mAbcg2 ( E, F ), or hABCG2 ( G, H ) cDNA. At t = 0 h ponatinib was added to the donor compartment; thereafter at t = 4 and 8 h the concentrations were measured and plotted as total amount (ng) of transport (n = 3). B, D-H : Zosuquidar (5 µM) or Ko143 (5 µM) were added as indicated to inhibit hABCB1 or hABCG2 and mAbcg2, respectively. r, relative transport ratio. BA (red squares, dashed line) translocation from the basolateral to the apical compartment; AB (blue circles), translocation from the apical to the basolateral compartment. Data are presented as mean ± SD. The curves were forced through the origin, assuming 0 transport at t = 0.