Table 2.
PopPK parameter estimates for vismodegib from the final model
| Parameter | Parameter description | Population estimate | Bootstrap final model median (2.5th, 97.5th percentiles) |
|---|---|---|---|
| exp(θ1) | Apparent clearance of unbound, CLunbound (L/day) | 1,326 | 1,332 (1,196, 1,467) |
| θ9 | Influence of age on CLunbound | −0.527 | −0.526 (−0.842, −0.248) |
| exp(θ2) | Apparent volume of distribution of central compartment, Vc (L) | 58.0 | 58.4 (53.2, 63.4) |
| θ10 | Influence of body weight on Vc | 0.660 | 0.65 (0.31, 0.96) |
| exp(θ3) | Dissociation constant, KDAAG (µM) | 0.056 | 0.056 (0.053, 0.058) |
| exp(θ6) | Relative bioavailability for Phase I formulation in patients (Phase II formulation as reference), F | 0.346 | 0.347 (0.293, 0.403) |
| θ7 | Influence of population on F | 0.881 | 0.880 (0.566, 1.33) |
| exp(θ4) | Absorption rate constant, ka (day−1) | 9.025 | 9.065 (6.870, 11.865) |
| θ5 | Influence of population on ka | 0.671 | 0.621 (0.215, 0.991) |
| θ8 | Influence of formulation on ka | −0.602 | −0.594 (−1.07, −0.11) |
| Intersubject variability (%) | CLunbound | 48.7 | 47.4 (39.6, 57.5) |
| Vc | 45.5 | 44.8 (39.7, 50.8) | |
| KDAAG | 19.7 | 19.5 (15.0, 23.2) | |
| Residual variability (%) | Total vismodegib plasma concentration | 26.7 | 26.5 (24.7, 28.6) |
| Unbound vismodegib plasma concentration | 42.4 | 42.3 (39.5, 44.9) |