Table 1.
Parameter estimates of the PK-PD model of pool data, where DA influences the maximum tumor cell-damaging effect constant kmax of AX with an interaction factor ψ
| Parameter (unit) | TV | IIV | ||
|---|---|---|---|---|
| Estimate | RSE (%) | CV (%) | RSE (%) | |
| ka (per day) | 78.7 FIX | — | 0 FIX | — |
| V/F (L/kg) | 16.5 FIX | — | 0 FIX | — |
| CL/F (L/kg/day) | 319 FIX | — | 0 FIX | — |
| N0 (mm3) | 50.4 | 7.2 | 29.3 | 15.8 |
| λ0 (per day) | 0.229 | 5.7 | 9.2 | 31.2 |
| λ1 (mm3/day) | 273 | 7.9 | 17.9 | 19.6 |
| kmax (per day) | 1.60 | 6.1 | 0 FIX | — |
| kC50 (mg/L) | 2.10 | 12.1 | 0 FIX | — |
| ψ | 2.43 | 8.8 | 0 FIX | — |
| σPRO (CV%) | 7.27 | 14.8 | — | — |
| σADD (mm3) | 31.5 | 10.1 | — | — |
N0, the initial tumor volume
λ0, the first-order growth rate constant of the exponential growth phase
λ1, the zero-order growth rate of the linear growth phase
kmax, the maximum effect constant of tumor cell damage
kC50, the AX concentration that reach the half of the maximum cell-damaging effect
ψ, the interaction factor characterizing the influence of DA on kmax of AX
σPRO, the SD of the proportional intra-individual variation
σADD, the SD of the additional intra-individual variation