Observed and predicted hepatic PSact,max values
PSact,max refers to the observed or predicted maximal transporter activity in hepatocytes. 1B1 and 1B3 determine OATP1B1 and OATP1B3, respectively. According to eqs. 3–7, the following scaling factors were used: relative expression factor (REF)1B1 = 0.853; REF1B3 = 0.181; relative activity factor (RAF)1B1 = 1.112; RAF1B3 = 0.113.
| Observed | REF-Based Scaling | RAF-Based Scaling | |||||
|---|---|---|---|---|---|---|---|
| PSact,max | PSact,max | PSact,max | |||||
| Total | 1B1 | 1B3 | 1B1 + 1B3 | 1B1 | 1B3 | 1B1 + 1B3 | |
| (µL/min/mg) | (µL/min/mg) | (µL/min/mg) | |||||
| E3S | 153.5a | 117.8 | 1.2 | 119.0 | n.a. | n.a. | n.a. |
| CCK8 | 8.6a | 0.0 | 13.8 | 13.8 | n.a. | n.a. | n.a. |
| Atorvastatin | 45.1 | 22.4 | 5.8 | 28.2 | 29.2 | 3.6 | 32.8 |
| Cerivastatin | 54.4 | 7.0 | 1.6 | 8.6 | 9.1 | 1.0 | 10.1 |
| Fluvastatin | 53.7 | 17.5 | 5.4 | 22.8 | 22.8 | 3.4 | 26.1 |
| Lovastatin | 40.6 | 7.6 | 0.0 | 7.6 | 9.9 | 0.0 | 9.9 |
| Pitavastatin | 89.5 | 28.6 | 2.6 | 31.2 | 37.2 | 1.6 | 38.9 |
| Pravastatin | 13.4 | 8.8 | 0.4 | 9.2 | 11.5 | 0.3 | 11.8 |
| Rosuvastatin | 6.7 | 4.5 | 0.7 | 5.3 | 5.9 | 0.5 | 6.4 |
| Simvastatin | 28.5 | 12.3 | 2.6 | 14.9 | 16.0 | 1.6 | 17.6 |
CCK8, cholecystokinin octapeptide; E3S, estrone-3-sulfate; n.a., not applicable.
↵a The value corresponds to the mean PSact,max derived from two independent experiments.