TABLE 4

NCA parameter comparison between actual PK- and PBPK-simulated data

MouseTissuet1/2 (h)AUC (h × μg/ml)t1/2 (Ratio)AUC (Ratio)
20 mg/kgBloodActual24.09 ± 8.8410.84 ± 0.631.870.97
Simulated12.9111.22
LiverActual3.38 ± 0.37116.93 ± 11.160.491.08
Simulated6.84107.9
KidneyActual15.12 ± 0.7272.25 ± 2.691.170.73
Simulated12.9699.01
GutActual20.45 ± 2.00100.55 ± 15.031.580.76
Simulated12.97131.80
40 mg/kgBloodActual11.2 ± 1.4919.50 ± 0.660.880.89
Simulated12.6721.89
LiverActual3.31 ± 0.17244.87 ± 33.980.551.24
Simulated6.00198.19
KidneyActual16.24 ± 1.24191.54 ± 12.561.271.09
Simulated12.74175.82
GutActual15.82 ± 3.20272.23 ± 18.751.241.22
Simulated12.76222.82
80 mg/kgBloodActual10.51 ± 0.5233.27 ± 2.250.840.75
Simulated12.4544.17
LiverActual4.03 ± 0.88512.92 ± 44.220.791.28
Simulated5.07400.70
KidneyActual13.77 ± 0.76339.17 ± 4.111.101.05
Simulated12.53322.20
GutActual16.04 ± 3.65432.80 ± 97.441.291.12
Simulated12.43385.13
Human
200 mg—Patient 4 (oral)BloodActual77.475.571.001.01
Simulated77.245.54
200 mg—Patient 4 (i.v.)BloodActual84.905.851.160.78
Simulated73.457.51
200 mg—Patient 1 (i.v.)BloodActual54.585.230.700.89
Simulated77.765.86
400 mg—Patient 1 (i.v.)BloodActual117.5010.011.720.80
Simulated68.2512.55