Drugs | PS_{inf} | PS_{u,inf} (+)^{c} | f_{B} ⋅ PS^{vitroe}_{u,inf} | Dispersion model | Well-stirred model | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

0% HSA^{a} | 5% HSA^{b} | 0% HSA | 5% HSA | f_{B}^{d} | 0% HSA | 5% HSA | R value^{f} | f_{B} ⋅ CL_{h,u,int,all}^{vivo}^{g} | Ratio^{h} (in vivo/in vitro) | f_{B} ⋅ PS^{vitro}_{u,inf} ⋅ SF at 5% HAS | f_{B} ⋅ CL_{h,u,int,all}^{vivo}^{g} | Ratio^{h} (in vivo/in vitro) | f_{B} ⋅ PS^{vitro}_{u,inf} ⋅ SF at 5% HAS | |

μl/min/10^{6} cells | μl/min/10^{6} cells | ml/min/kg | ml/min/kg | ml/min/kg^{g} | ml/min per kilogram | ml/min per kilogram | ||||||||

Pitavastatin | 36.2 | 0.493 | 36.2 | 88.3 | 0.00932 | 1.04 | 2.54 | 2.44 | 14.1 | 5.57 | 6.20 | 18.0 | 7.11 | 8.11 |

Atorvastatin | 24.2 | 2.16 | 24.2 | 77.0 | 0.0467 | 3.48 | 11.1 | 3.18 | 25.3 | 2.28 | 27.1 | 39.1 | 3.53 | 35.4 |

Rosuvastatin^{g} | 4.01 | 0.983 | 4.01 | 9.94 | 0.195 | 2.41 | 5.98 | 2.48 | 20.6 | 3.44 | 14.6 | 29.2 | 4.89 | 19.1 |

Fluvastatin | 62.1 | 1.72 | 62.1 | 424 | 0.00690 | 1.32 | 9.03 | 6.83 | 27.3 | 3.02 | 22.1 | 43.6 | 4.83 | 28.8 |

Cerivastatin | 77.5 | 2.31 | 77.5 | 240 | 0.0127 | 3.02 | 9.37 | 3.10 | 5.96 | 0.636 | 22.9 | 6.59 | 0.703 | 29.9 |

Pravastatin | 3.55 | NA | 3.55 | NA | 1.00 | 11.0 | NA | NA | 22.9 | NA | NA | 33.9 | NA | NA |

Glibenclamide | 32.2 | 0.155 | 32.2 | 173 | 0.00171 | 0.170 | 0.912 | 5.38 | 2.47 | 2.71 | 2.23 | 2.58 | 2.83 | 2.91 |

Valsartan | 1.87 | 0.0514 | 1.87 | 119 | 0.00301 | 0.0174 | 1.11 | 63.8 | 0.698 | 0.630 | 2.71 | 0.701 | 0.633 | 3.54 |

Repaglinide | 39.2 | 2.48 | 39.2 | 207 | 0.0109 | 1.32 | 6.95 | 5.27 | 19.0 | 2.72 | 17.0 | 26.3 | 3.78 | 22.2 |

Bosentan | 23.2 | 1.24 | 23.2 | 113 | 0.00981 | 0.703 | 3.41 | 4.86 | 3.14 | 0.919 | 8.34 | 3.31 | 0.969 | 10.9 |

Nateglinide | 12.5 | 0.282 | 12.5 | 43.9 | 0.00994 | 0.382 | 1.35 | 3.52 | 3.37 | 2.50 | 3.29 | 3.58 | 2.66 | 4.30 |

*CL*_{h,u,int,all}, the in vivo unbound hepatic intrinsic clearance;*f*_{B}, blood-unbound fraction; NA, not applicable;*PS*_{inf}, the hepatic uptake clearance for total drug;*PS*_{u,inf}, the hepatic uptake clearance for unbound drug;*SF*, Scaling factor.↵

Obtained mean value from the suspended hepatocyte uptake study without HSA (^{a}↵

Predicted by Tsao’s model in the presence of 5% HSA using the observed data at 0–1% HSA (eq. 5; Table 1).^{b}↵

Calculated by dividing^{c}*PS*_{inf}by*f*_{u}, where*f*_{u}is 1 in the absence of HSA.↵

Calculated by dividing^{d}*f*_{p}by*R*_{B}, where*R*_{B}is the blood partitioning.↵

Scaled-up from in vitro^{e}*PS*_{u,inf}(+) using the following physiologic scaling factors (1.2 × 10^{8}cells/g of liver, 25.7 g of liver/kg of body weight).↵

^{f}*R*values, the “albumin-mediated” uptake factor, was calculated as the ratio of*f*_{B}⋅*PS*^{vitro}_{u,inf}at 0% HSA to that at 5% HSA.↵

These data were calculated using the dispersion model or the well-stirred model using the reported hepatic clearance. The details are shown in Supplemental Table S3.^{g}↵

Calculated by^{h}*f*_{B}⋅*CL*^{vivo}_{h,u,int,all}/*f*_{B}⋅*PS*^{vitro}_{u,inf}at 5% HSA; the mean value is 2.44 for the dispersion model and 3.19 for the well-stirred model, which was used as the scaling factor (*SF*).