Table 3.
Population pharmacokinetic parameters obtained from the base (no covariates and no dose normalization), weight normalized dosing, and the final covariate model with sex and weight normalized dosing.
| Parameter | Base Estimate |
RSE (%) |
WT Normalized Estimate |
RSE (%) |
p-value | Sex WT Normalized Estimate |
RSE (%) |
p- value |
| CL (L/hr; mL/hr/kg) |
0.071 | 10 | 1.27 | 6 | 1.20 | 10 | ||
| β: Sex* | 0.16 | 58 | 0.08 | |||||
| V1 (L; mL/kg) | 3.51 | 10 | 61.61 | 4 | 57.05 | 5 | ||
| β: Sex* | 0.16 | 46 | 0.03 | |||||
| Q (L/hr; mL/hr/kg) |
0.075 | 8 | 1.12 | 5 | 1.07 | 5 | ||
| V2 (L; mL/kg) | 6.21 | 26 | 100.61 | 20 | 91.54 | 33 | ||
| CLM (L/hr; L/hr/kg) |
106.30 | 13 | 1.96 | 9 | 2.01 | 12 | ||
| VM (L; L/kg) | 2626.61 | 13 | 48.37 | 8 | 48.41 | 10 | ||
| ADC σ prop (CV%) |
4.6 | 264 | 6.9 | 52 | 7.6 | 41 | ||
| MMAE σ prop (CV%) |
31 | 19 | 29 | 18 | 30 | 18 | ||
| −2 Log- likelihood |
888.5 | 796.8 | <1e-10 | 790.2 | <0.04 | |||
| IIV | (CV%) | RSE (%) |
(CV%) | RSE (%) |
(CV%) | RSE (%) |
||
| CL | 34 | 21 | 17 | 24 | 16 | 24 | ||
| V1 | 38 | 18 | 15 | 24 | 12 | 28 | ||
| Q | 14 | 99 | 6 | 339 | 5 | 478 | ||
| V2 | 74 | 23 | 44 | 34 | 27 | 105 | ||
| CLM | 40 | 24 | 25 | 30 | 26 | 29 | ||
| VM | 38 | 32 | 9 | 248 | 8 | 373 |
*
Covariate model: θ*exp(β*covariate) where covariate=[0−Female or 1−Male]