Table 2.
Parameter estimates and bootstrap analysis for the final model for free SN-38
| Parametera | Final model estimatea (%RSE) | Bootstrap analysis median value (95% CI) | Untransformed estimate |
|---|---|---|---|
| Log (KREL), 1/h | –2.34 (2.61) | –2.35 (–2.48 to –2.22) | 0.0961 L/h |
| Log (CLSN38/F), L/h | 6.02 (1.05) | 6.00 (5.89 to 6.13) | 409 L/h |
| Log(QSN38/F), L/h | 5.51 (0.466) | 5.51 (5.34 to 5.70) | 247 L/h |
| V1SN38/F, L | 49a (Fixed) | ||
| V2SN38/F, L | 2177a (Fixed) | ||
| IIV variance for KRELb | 0.332 (12.6) | 0.341 (0.258 to 0.430) | |
| IIV variance for CLSN38/Fc | 0.411 (14.6) | 0.412 (0.299 to 0.555) | |
| Weight exponent on CLSN38/F and QSN38/F | 0.500 (13.3) | 0.494 (0.355 to 0.648) | |
| Time after last dose on RUV | 0.011 (12.2) | 0.011 (0.009 to 0.013) | |
| Study IMMU-132-01 on RUV | –0.230 (19.4) | –0.224 (–0.361 to 0.038) | |
| Log RUV SD on LOG SN-38 | –1.03 (8.37) | –1.05 (–1.33 to –0.860) | 0.357 |
| KREL ~ CLSN38/F covariance | 0.269 (16.20) | 0.274 (0.191 to 0.370) |
%RSE relative standard error in percent, CI confidence interval, CLSN38/F apparent clearance of free SN-38, IIV interindividual variability, KREL first-order sacituzumab govitecan release rate, QSN38/F apparent intercompartmental clearance of free SN-38, RUV residual unexplained variability, SD standard deviation, V1SN38/F apparent central volume of distribution of free SN-38, V2SN38/F apparent peripheral volume of distribution of free SN-38
aV1SN38/F and V2SN38/F parameters were fixed to literature values to ensure identifiability of the model
bShrinkage for IIV variance for KREL was 29.3%
cShrinkage for IIV variance for CLSN38/F was 39.6%