Stephanie van Hoppe

92 Chapter 4 Supplemental Figure 1 - Schematic representation of the formation of ibrutinib-DiOH from ibrutinib. The main active ibrutinib metabolite, ibrutinib-DiOH (DiOH) is formed by Cytochrome P450 (primarily CYP3A4). Supplemental Figure 2 - Plasma concentration−time curves of ibrutinib (A) and ibrutinib-DiOH (DiOH) (B) and in femaleWT (black circles) and Abcb1a/1b;Abcg2 −/− (green squares) mice over 8 h after oral administration of 10 mg/kg ibrutinib. When the 8 h data were below the lower limit of quantification, data were only plotted up till 3 h. Note the different concentration scales in panels A and B. Data are given as mean ± SD. n = 5−6 mice per group. Supplemental Figure 1. Schematic representation of t e formation of ibrutini -DiOH from ibrutinib. The main active ibrutinib metabolite, ibrutinib-DiOH (DiOH) is formed by Cytochrome P450 (primarily CYP3A4). Supplemental Figure 2 . Plasma concentration−time curves of ibrutinib (A) and ibrutinib-DiOH (Di (B) and in female WT (black circles) and Abc 1a/1b;Abcg2 −/− (green squares) mice over 8 h after o dministr tion of 10 mg/kg i rutinib. When the 8 h data were below the lower limit of quantificati data were only plotted up till 3 h. Note t e different concentration scales in panels A and B. Data given as mean ± SD. n = 5−6 mic per group. A B 0 2 4 6 8 1 10 100 1000 0 2 4 6 8 0 500 1000 1500 2000 2500 Time (hours) DiOH ng/ml Wild Type Abcb1a/1b;Abcg2-/- 0 2 4 6 8 1 10 100 1000 10000 0 2 4 6 8 0 200 400 600 800 1000 Time (hours) Ibrutinib concentration ng/ml Wild Type Abcb1a/1b; Abcg2-/-