TABLE 4

Kp,uu,ss and fT,cell,ss in human hepatocytes

Values are shown as the mean ± S.D. (n = 3).

DrugLotC/M RatiocKp,uu,ssdfT,cell,ssd
37°COn ice
DiazepamHu8075a216 ± 20181 ± 381.19 ± 0.510.00553 ± 0.00115
TFFb124 ± 53303 ± 220.409 ± 0.2470.00330 ± 0.00024
PitavastatinHu8075a471 ± 8835.2 ± 2.613.4 ± 2.70.0284 ± 0.0021
TFFb150 ± 2.621.8 ± 3.26.92 ± 1.020.0460 ± 0.0068
RosuvastatinHu8075a52.2 ± 8.64.51 ± 0.4111.6 ± 2.20.222 ± 0.020
TFFb27.2 ± 2.54.28 ± 0.536.36 ± 1.060.234 ± 0.029
PravastatinHu8075a3.73 ± 0.731.84 ± 0.122.03 ± 0.540.545 ± 0.035
TFFb2.65 ± 1.292.07 ± 0.641.28 ± 0.890.484 ± 0.151
  • a Isolated cryopreserved human hepatocytes (Lot Hu8075) were incubated with diazepam (0.2 µM), pitavastatin (0.1 µM), rosuvastatin (0.1 µM), and pravastatin (0.2 µM).

  • b Pooled cryopreserved human hepatocytes from 20 mixed-sex donors (Lot TFF) were incubated with diazepam (1 µM), pitavastatin (0.5 µM), rosuvastatin (0.5 µM), and pravastatin (1 µM).

  • c C/M ratios at 37°C and on ice were calculated using the uptake data at 30 minutes and 60 minutes, respectively (Fig. 2).

  • d The Kp,uu,ss and fT,cell,ss were calculated from C/M ratios using eqs. 2 and 3, respectively.