Table 3.
Parameter estimates from the population pharmacokinetic final model for trials 1, 2 and 3
| Structural model: | |||
| CL/F = θCL × (WT/70)0.75 × (AAG/20.0)θAAG_CL × eηCL | |||
| V/F = θV × (WT/70) × (AAG/20.0)θAAG_V × eηV | |||
| Ka = θKa × eηKa, ALAG1 = θALAG1 | |||
| Residual random effect model: | |||
| Y = Ŷ + Ŷ × ε1 + ε2 | |||
| Parameter | Estimate | %RSE | Description |
| CL/F (l h−1) | 2.28 | 4.21 | Apparent clearance |
| θAAG_CL | −0.844 | −15.1 | Effect of AAG on the apparent clearance |
| V/F (l) | 37.5 | 6.35 | Apparent volume of distribution |
| θAAG_V | −0.663 | −24.3 | Effect of AAG on the apparent volume of distribution |
| Ka (h−1) | 0.368 | 12.0 | First order absorption rate constant |
| ALAG1 (h) | 0.957 | 1.14 | Absorption lag time |
| IIV in CL/F (CV%) | 54.4 | 11.4a | Inter-individual variability in the apparent clearance |
| IIV in V/F (CV%) | 61.2 | 17.7a | Inter-individual variability in the apparent volume of distribution |
| IIV in Ka (CV%) | 117 | 19.7a | Inter-individual variability in the first order absorption rate constant |
| Cov_V/CL | 0.238 | 16.7a | Covariance between inter-individual variability in the apparent clearance and inter-individual variability in the apparent volume of distribution. The estimate translates to a coefficient of correlation of 0.715 |
| Proportional residual variability (CV%) | 28.4 | 6.13b | |
| Additive residual variability (SD ng ml−1) | 0.178 | 27.0b | |
a
SE is given on the variance scale.
b
SE was derived by coding the residual error using THETAs.