Table 4.
Rat and human empirical plasma PK models used as input to LeiCNS-PK3.0 model
| Plasma PK parameter estimates | Interindividual variability | Residual variability | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clcen (mL min−1) | Qcen-per1 (mL min−1) | Qcen-per2 (mL min−1) | Vcen (mL) | Vper1 (mL) | Vper2 (mL) | Clcen (%) | Qcen-per1 (%) | Qcen-per2 (%) | Vcen (%) | Vper1 (%) | Vper2 (%) | Proportional (%) | Additive (ng mL−1) | |
| Rat plasma PK models | ||||||||||||||
| Acetaminophen | 4.70 | 11.18 | 31.35 | 50.71 | 27,891.70 | 162.47 | 35.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 26.7 | 0.0 |
| Atenolol | 6.30 | 4.25 | 0.0 | 118.70 | 203.36 | 0.0 | 8.9 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.7 | 0.0 |
| Methotrexate | 8.31 | 23.33 | 0.79 | 38.16 | 139.95 | 47.99 | 36.5 | 0.0 | 52.3 | 0.0 | 0.0 | 29.5 | 17.6 | 0.0 |
| Morphine | 23.34 | 4.97 | 31.68 | 175.73 | 1636.28 | 475.86 | 46.9 | 93.9 | 0.0 | 92.5 | 0.0 | 49.2 | 24.2 | 0.0 |
| Paliperidone | 219.46 | 6765.63 | 0.0 | 25.00 | 32,981.00 | 0.0 | 44.4 | 0.0 | 0.0 | 0.0 | 45.5 | 0.0 | 20.0 | 0.0 |
| Phenytoin | 47.72 | 415.88 | 0.0 | 453.32 | 2268.39 | 0.0 | 65.8 | 0.0 | 0.0 | 122.5 | 22.0 | 0.0 | 16.3 | 1571.0 |
| Quinidine | 178.28 | 238.03 | 753.99 | 183.65 | 7335.00 | 5062.54 | 26.1 | 38.4 | 0.0 | 0.0 | 0.0 | 0.0 | 23.4 | 20.8 |
| Raclopride | 45.40 | 68.04 | 15.03 | 50.44 | 468.42 | 690.00 | 13.6 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.3 | 0.0 |
| Remoxipride | 47.43 | 16.52 | 56.76 | 82.89 | 602.77 | 457.52 | 31.0 | 0.0 | 29.8 | 124.4 | 36.4 | 44.7 | 21.3 | 0.0 |
| Risperidone | 773.30 | 0.0 | 0.0 | 47,936.80 | 0.0 | 0.0 | 89.9 | 0.0 | 0.0 | 66.9 | 0.0 | 0.0 | 29.6 | 12.9 |
| Human plasma PK models | ||||||||||||||
| Acetaminophen | 495.00 | 0.0 | 0.0 | 108,000.00 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 23.9 | 0.0 |
| Indomethacina | 14,200.00 | 54,600.00 | 0.0 | 1,320,000.00 | 10,300,000.00 | 0.0 | 0.0 | 145.9 | 0.0 | 0.0 | 0.0 | 0.0 | 22.3 | 0.0 |
| Morphine | 3070.00 | 3030.00 | 0.0 | 16,000.00 | 95,400.00 | 0.0 | 27.1 | 0.0 | 0.0 | 59.6 | 0.0 | 0.0 | 9.6 | 0.0 |
| Oxycodone | 1140.00 | 11,700.00 | 47.40 | 93,600.00 | 178,000.00 | 19,400.00 | 31.1 | 0.0 | 0.0 | 86.7 | 0.0 | 0.0 | 19.1 | 0.0 |
aIntramuscular dosing was used with bioavailability of 100% [70] and estimated absorption rate constant of 2,850,000 (min−1)