Table 3.
Key pharmacokinetic parameters
| Cmax (ng/mL) | AUC∞ (day × ng/mL) | Clearance (mL/day/kg) | V1 (mL/kg) | V2 (mL/kg) | Vss (mL/kg) | α Half-life (day) | β Half-life (day) | K10 Half-life (day) | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Cohort 3 (3.0 mg/kg) | N | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
| Mean | 43 309 | 465 218 | 6.542 | 67.25 | 67.18 | 134.4 | 0.6514 | 15.00 | 7.266 | |
| SD | 2,978 | 70 169 | 0.9330 | 3.552 | 46.10 | 42.55 | 0.4147 | 3.637 | 1.498 | |
| CV% | 6.9 | 15.1 | 14.3 | 5.3 | 68.6 | 31.7 | 63.7 | 24.2 | 20.6 | |
| Cohort 4 (6.0 mg/kg) | N | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
| Mean | 102 363 | 880 104 | 6.99 | 56.45 | 30.74 | 87.19 | 0.7944 | 9.496 | 5.791 | |
| SD | 9,668 | 173 357 | 1.323 | 7.714 | 7.721 | 8.557 | 0.6252 | 3.169 | 1.595 | |
| CV% | 9.4 | 19.7 | 18.9 | 13.7 | 25.1 | 9.8 | 78.7 | 33.4 | 27.5 | |
| Cohort 5 (9.0 mg/kg) | N | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
| Mean | 132 687 | 1 462 480 | 6.758 | 68.80 | 31.57 | 100.4 | 1.981 | 12.37 | 7.340 | |
| SD | 23 721 | 541 763 | 2.173 | 13.01 | 6.192 | 8.758 | 1.756 | 2.461 | 1.419 | |
| CV% | 17.9 | 37.0 | 32.2 | 18.9 | 19.6 | 8.7 | 88.6 | 19.9 | 19.3 | |
| Cohort 6 (12.0 mg/kg) | N | 16 | 16 | 16 | 16 | 16 | 16 | 16 | 16 | 16 |
| Mean | 169 279 | 1 791 460 | 7.192 | 71.43 | 58.56 | 130.0 | 0.9119 | 14.12 | 7.237 | |
| SD | 35.891 | 480.648 | 2.088 | 16.50 | 20.09 | 33.34 | 0.4420 | 4.691 | 2.134 | |
| CV% | 21.2 | 26.8 | 29.0 | 23.1 | 34.3 | 25.6 | 48.5 | 33.2 | 29.5 |
CV%, coefficient of variation percent; K10, first order elimination rate constant; V1, volume of compartment 1; V2, volume of compartment 2; Vss, volume of distribution at steady state.
Cmax and AUC∞ are model-predicted values following a single dose at the given dose level and are not observed Cmax and dose interval AUC.