Table 2.
Parameter estimates following fitting of the PK–PD model describing pAkt modulation for patients with advanced solid tumors (phase 1 studies)
| Parameter | Unit | Estimate | RSE% | Shrinkage% |
|---|---|---|---|---|
| IC50 | μg/L | 9.32 | 12.7 | – |
| kin | %/h | 88,699 | 3.8 | – |
| kout* | 1/h | 886.99 | – | – |
| Imax | – | 1 (fix) | – | – |
| γ1** | – | 1 (fix) | – | – |
| Proportional error | – | 0.672 | 9.5 | – |
| IIV IC50 | Variance | 0.296 | 44.3 | 15.5 |
γ1, sigmoidicity factor; Imax, maximum inhibition of %pAkt; kin, rate of biomarker production; kout, first-order rate constant describing biomarker loss; IC50, half maximal inhibitory concentration; t, time; and Cp, plasma concentration
*kout = kin/%pAkt(0), where %pAkt(0) is the baseline %pAkt at time zero = 100%
**Sigmoidicity parameter estimate was 0.868–0.937; therefore it was fixed to 1 in the final model