Table 5.
Population parameters of the final population pharmacokinetic model
| Pharmacokinetic parameters | Units | Estimate | RSE (%) |
|---|---|---|---|
| V1 | l | 10.2 | 15.3 |
| V3 | l | 642 | 19.7 |
| VMEL | µmol h−1 | 6.4 | 17.3 |
| KMEL | µmol l−1 | 0.06 | 35.0 |
| VMTR | µmol h−1 | 161 | 13.2 |
| KMTR | µmol l−1 | 0.55 | 13.4 |
| K21 | h−1 | 1.20 | 12.5 |
| Q | l h−1 | 16.1 | 8.82 |
| Interindividual variability | |||
| VMEL | % | 33.4 | 17.3 |
| VMTR | % | 22.2 | 17.9 |
| Residual variability* | |||
| Subpopulation 1 | % | 52.2 | 19.7 |
| Subpopulation 2 | % | 25.0 | 13.2 |
| Pharmacodynamic parameters | |||
| MTT (ANC) | h | 62.8 | NA |
| MTT (PLT) | h | 50.8 | 10.0 |
| γ (feedback ANC) | 0.11 | NA | |
| γ (feedback PLT) | 0.07 | 18.5 | |
| Slope (ANC) | l µmol−1 | 1.85 | NA |
| Slope (PLT) | l µmol−1 | 0.25 | 22.3 |
| Total bilirubin on slope (ANC) | 0.022 | NA | |
| Total bilirubin on slope (PLT) | 0.017 | 34.3 | |
| Interindividual variability | |||
| MTT (ANC) | % | 45.5 | NA |
| MTT (PLT) | % | 13.7 | 10.5 |
| Slope (ANC) | % | 34.7 | NA |
| Slope (PLT) | % | 57.0 | 37.9 |
| CV on baseline ANC | % | 67.0 | NA |
| CV on baseline PLT | % | 25.8 | 9.0 |
V1, Volume of the central compartment; V3, volume of the second peripheral compartment; VMEL, maximal elimination rate; KMEL, plasma concentration at half VMEL; VMTR, maximal transport rate from the central to the first peripheral compartment; KMTR, plasma concentration at half VMTR; K21, rate constant from the first peripheral compartment to the central compartment; Q, intercompartmental clearance between the central and second peripheral compartment; RSE, relative standard error (as obtained from the covariance step).
Fraction subgroup one 0.32 (RSE = 28.1%). MTT, Median transition time (h); γ, feedback, implemented in (ANCbase/ANCt)γ; slope, linear drug effect parameter; CV, coefficient of variation; NA, not available (resulting from failed variance–covariance step).