Stephanie van Hoppe

76 Chapter 4 Figure 1. In vitro transport of ibrutinib. Transepithelial transport of ibrutinib (2 μM) was assessed in MDCK-II cells either nontransduced ( A, B ) or transduced with hABCB1 ( C, D ), mAbcg2 ( E, F ), or hABCG2 ( G, H ) cDNA. At t = 0 h ibrutinib was added to the donor compartment; thereafter at t = 1, 2 and 4 h the concentrations were measured and plotted as total amount (pmol) of translocated drug (n = 3). ( B, D−H ) Zosuquidar (Zos, 5 μM) or Ko143 (5 μM) were added as indicated to inhibit hABCB1 or hABCG2 and mAbcg2, respectively. r, relative transport ratio at 4 h. BA (blue squares) translocation 0 1 2 3 4 5 0 200 400 600 800 Time (hours) Ibrutinib transport (pmol) Parental 0 1 2 3 4 5 0 200 400 600 800 hABCB1 Time (hours) Ibrutinib transport (pmol) 0 1 2 3 4 5 0 200 400 600 800 Time (hours) Ibrutinib transport (pmol) hABCG2 + Zos 0 1 2 3 4 5 0 200 400 600 800 Time (hours) Ibrutinib transport (pmol) mAbcg2 + Zos 0 1 2 3 4 5 0 200 400 600 800 Time (hours) Ibrutinib transport (pmol) Parental + Zos AB BA 0 1 2 3 4 5 0 200 400 600 800 Time (hours) Ibrutinib transport (pmol) hABCB1 + Zos AB BA 0 1 2 3 4 5 0 200 400 600 800 Time (hours) Ibrutinib transport (pmol) hABCG2 + Ko143 + Zos AB BA 0 1 2 3 4 5 0 200 400 600 800 Time (hours) Ibrutinib transport (pmol) mAbcg2 + Ko143 + Zos AB BA r = 1.05 r = 0.9 r = 2.0 r = 1.1 r = 0.9 r = 0.8 r = 1.8 r = 1.1 A B C D E F G H Figure 1 - In vitro transport of ibrutinib. Transepithelial transport of ibrutinib (2 μM) was assessed in MDCK-II cells either nontransduced ( A, B ) or transduced with hABCB1 ( C, D ), mAbcg2 ( E, F ), or hABCG2 ( G, H ) cDNA. At t = 0 h ibrutinib was added to the donor compartment; thereafter at t = 1, 2 and 4 h the concentrations were measured and plotted as total amount (pmol) of translocated drug (n = 3). ( B, D−H ) Zosuquidar (Zos, 5 μM) o Ko143 (5 μM) were added as indica ed t inhibit hABCB1 or hABCG2 and mAbcg2, respectively. r, relative transport ratio at 4 h. BA (blue squares) 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.