Table 3.
Final parameter estimates and bootstrap outcomes
| Parameter | Unit | Description | Population typical value | Between-subject variability | ||
|---|---|---|---|---|---|---|
| Estimate | Bootstrap median (95 % CI) | Estimate (as CV%) | Bootstrap median (95 % CI) | |||
| Pharmacokinetic parameters | ||||||
| CL | L/h·m2 | Clearance | 87.8 | 88.3 (72.2–108) | 21.4 | 20.5 (13.0–26.8) |
| V c | L/m2 | Volume of central compartment | 18.5 | 18.2 (14.2–23.5) | NE | NE |
| V p | L/m2 | Volume of peripheral compartment | 22.9 | 21.9 (15.7–46.1) | NE | NE |
| Q | L/h·m2 | Intercompartmental clearance | 13.1 | 13.3 (10.0–19.6) | NE | NE |
| Pharmacodynamic parameters for platelet | ||||||
| k tr,P | h−1 | Rate constant of inter-compartmental platelet movement | 0.0244 | 0.0246 (0.0236–0.0254) | NE | NE |
| SLOPE P | – | Drug effect on platelet count | 0.0656 | 0.0676 (0.0539–0.0930) | 25.7 | 20.8 (1.30–56.0) |
| BASE P | /mm3 | Baseline platelet count | 49,200 | 53,700 (36,100–95,800) | 105 | 78.3 (38.3–110) |
| GAMMA P | – | Shape factor for platelet count fluctuation | 0.304 | 0.299 (0.264–0.325) | NE | NE |
| IMP | Maximum degree of platelet count recovery expected | 55000 | 58700 (24200 – 98300) | 78.3 | 72.9 (19.5 – 150) | |
| IMK | Rate constant for asymptotic platelet count recovery | 0.000530 | 0.000513 (0.000213–0.000691) | NE | NE | |
| Pharmacodynamic parameters for neutrophil | ||||||
| k tr,N | h−1 | Rate constant of inter-compartmental neutrophil movement | 0.0132 | 0.0133 (0.0120–0.0139) | NE | NE |
| SLOPE N | – | Drug effect on neutrophil count | 0.263 | 0.237 (0.114–0.363) | 57.5 | 58.1 (25.8–119) |
| BASE N | /mm3 | Baseline neutrophil count | 3240 | 3015 (2110–4140) | 43.5 | 40.6 (27.2–57.6) |
| GAMMA N | – | Shape factor for neutrophil count fluctuation | 0.193 | 0.181 (0.110–0.251) | 39.4 | 36.7 (15.0–65.4) |
| Residual error | ||||||
| σ PK 2 | – | Variance of residual error (proportional) for PK | 0.441 | 0.436 (0.354–0.505) | – | – |
| σ PD,P 2 | Variance of residual error (additive) for platelet count | 25,000 | 24,300 (18,800–29,600) | – | – | |
| σ PD,N 2 | Variance of residual error (additive) for neutrophil count | 754 | 748 (613–839) | – | – | |
Proportion of successful convergence: 78.8 % for PK model, 78.0 % for PD model
NE not estimated