PBPK model parameters
PBPK model parameters that were adjusted using literature data to plasma concentration and urinary excretion of pravastatin after intravenous and oral doses of 9.9 and 40 mg, respectively (Singhvi et al., 1990; Mwinyi et al., 2004). Clearance processes (CLx) are given as specific clearance rates (liters per minute), which can be calculated from intrinsic clearance rates (milliliters per minute) by normalization to the volume of the compartment or organ in which metabolism or degradation takes place.
| Parameter | Basic | Basic Extended | Array | RT-PCR | EST | Best Random | Worst Random |
|---|---|---|---|---|---|---|---|
| Lipophilicity | 1.00 | 1.00 | 0.84 | 0.79 | 0.99 | 0.60 | 1.1 |
| Pint, cm/min | 3.5 × 10−3 | 3.50 × 10−3 | 8.3 × 10−3 | 6.4 × 10−3 | 7.0 × 10−3 | 5.9 × 10−3 | 1.4 × 10−2 |
| CLhep, l/min | 22.6 | 22.6 | |||||
| CLren, l/min | 7.4 × 10−2 | 2.5 × 10−1 | |||||
| CLdegrad, l/min | 0.020 | 0.010 | 0.010 | 0.014 | 0.020 | 0.010 | |
| k*cat,OATP1B1, μmol · −1 · min−1 | 4.2 × 102 | 6.2 × 10−1 | 1.1 × 103 | 7.0 × 102 | 2.1 × 102 | 1.6 × 10−1 | |
| k*cat, OAT3, μmol · −1 · min−1 | 5.8 × 105 | 3.4 × 106 | 3.4 × 106 | 3.4 × 104 | 8.7 × 105 | ||
| k*cat,MRP2, μmol · −1 · min−1 | 2.7 | 1.4 | 2.3 | 0.1 | 145 | ||
| k*cat, SULT, μmol · −1 · min−1 | 0.6 | 4.6 | 2.8 | 4.9 | 2.3 × 10−4 |