Intrinsic clearance in Ad-P450 HepG2 cells and suspended cryopreserved hepatocytes and comparison with in vivo intrinsic clearance
| P450 | Substrate | RAFa | Scaled Ad-P450 CLintb | Hepatocyte CLintc | Ad-P450 Predicted CLintd | Hepatocyte Predicted CLintd | In Vivo Observed CLintc |
|---|---|---|---|---|---|---|---|
| μl/(min·106 hepatocytes) | ml/(min·kg) | ||||||
| CYP1A2 | Phenacetin | 2.1 | 83.2 | 13.5 | 214 | 34.7 | 615 |
| CYP2C9 | Tolbutamide | 0.29 | 0.679 | 0.148 | 1.74 | 0.38 | 3.6 |
| CYP3A4 | Alprazolam | 0.98 | 2.13 | 0.818 | 5.47 | 2.1 | 3.7 |
| CYP3A4 | Midazolam | 0.46 | 23.2 | 77.9 | 59.6 | 200 | 314 |
↵a RAF based on a ratio of marker activities (7-ethoxyresorufin O-deethylation, diclofenac 4′-hydroxylation, or testosterone 6β-hydroxylation) in human cultured hepatocytes and Ad-P450-transduced HepG2 cells.
↵b Scaled using RAF for the primary cultured human hepatocytes.
↵c Data from Brown et al. (2007) (tolbutamide, alprazolam, and midazolam) and Stringer et al. (2008) (phenacetin).
↵d Scaled using a hepatocellularity of 120 × 106 hepatocytes/g and liver weight of 21.4 g/kg and based on human cryopreserved hepatocytes.