Stephanie van Hoppe

90 Chapter 4 S U P P L EME N TA L MAT E R I A L Supplemental Table 1 - Pharmacokinetic parameters of ibrutinib-DiOH at 8 h and 1 h minutes after oral administration of 10 mg/kg ibrutinib to female WT, Abcb1a/1b -/- , Abcg2 -/- and Abcb1a/1b;Abcg2 -/- mice. Parameter Genotype Time WT Abcb1a/1b -/- Abcg2 -/- Abcb1a/1b;Abcg2 -/- AUC 0-8 (ng/ml.h) 8 h 3423 ± 213 3427 ± 450 C max (ng/ml) 1779 ± 65 2220 ± 146 T max (minutes) 21 ± 8 18 ± 7 AUC 0-1 (ng/ml.h) 1 h 992 ± 105 783 ± 86 ** 752 ± 73 ** 633 ± 92 **** C max (ng/ml) 1422 ± 295 1118 ± 315 1032 ± 205 888 ± 336 T max (minutes) 13 ± 3 10 ± 2 12 ± 3 16 ± 8 C brain (ng/g) 16.0 ± 4.1 39.7 ± 8.6 ** 13.1 ± 2.8 ### 45.1 ± 14.3 *** Brain to plasma ratio 0.005 ± 0.003 0.063 ± 0.020 **** 0.009 ± 0.004 #### 0.077 ± 0.018 **** Fold change 1 12.6 1.8 15.4 C liver (ng/g) 733 ± 178 660 ± 101 485 ± 40 * 503 ± 137 * Liver to plasma ratio 1.233 ± 0.168 1.434 ± 0.260 1.106 ± 0.107 1.120 ± 0.150 Fold change 1 1.2 0.9 0.9 Brain to liver ratio 0.022 ± 0.002 0.060 ± 0.011 **** / ### 0.027 ± 0.004 #### 0.089 ± 0.011 **** Fold change 1 2.7 1.2 4 AUC, area under the plasma concentration-time curve; C max maximum ibrutinib-DiOH concentration in plasma; T max , the time (min) after drug administration needed to reach maximum plasma concentration; C brain , brain concentration; C liver , liver concentration. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 compared to WT mice and #, P < 0.05; ##, P < 0.01; ###, P < 0.001 compared to Abcb1a/1b;Abcg2 -/- mice. Data are given as mean ± SD.