Table 2.
Population PK model parameter estimates
| Parametera | Population mean |
Magnitude of IIV |
||
|---|---|---|---|---|
| estimate | SEM (%) | estimate | SEM (%) | |
| Plasma | ||||
| CL (L/h) | 159 | 5.61 | 16.1 | 57.7 |
| Vc (L) | 53.1 | 9.66 | 13.4 | fixed |
| CLD1 (L/h) | 86.6 | 42.1 | 37.1 | 77.5 |
| Vp1 (L) | 656 | 27.4 | 24.7 | fixed |
| CLD2 (L/h) | 199 | 16.1 | 23.5 | 69.1 |
| Vp2 (L) | 259 | 8.17 | NE | N/A |
| Ka (1/h) | 1.20 | 11.6 | 108.2 | 38.5 |
| Ka2 (1/h) | 2.12 | 26.0 | 54.8 | 63.3 |
| Ftot | 0.24 | 7.99 | 22.8 | 84.6 |
| FS | 0.80 | 8.35 | 55.7 | 74.2 |
| proportion of Ka when fed | 0.04 | 14.7 | NE | NA |
| proportion of Ka2 when fed | 0.44 | 3.55 | NE | NA |
| proportion of Ftot when fed | 0.81 | 9.13 | NE | NA |
| ELF | ||||
| Kin (1/h) | 2.71 | 17.0 | 31.6 | fixed |
| Kout (1/h) | 0.51 | 27.5 | 31.6 | fixed |
| Protein binding | ||||
| Fumin | 0.0997 | |||
| Fumax | 0.259 | |||
| Cup50 (mg/L) | 1.35 | |||
| RV | ||||
| plasma proportional error | 0.007 | 9.48 | NE | NA |
| ELF proportional error | 0.05 | fixed | NE | NA |
CL, total clearance of free drug; CLD1, distributional clearance to first peripheral compartment; CLD2, distributional clearance to second peripheral compartment; Cup50, concentration at which protein binding is half-maximal; Fumax, maximum extent of non-linear protein binding; Fumin, minimum extent of non-linear protein binding; NA, not applicable; NE, not evaluated; Vp1, volume of first peripheral compartment; Vp2, volume of second peripheral compartment.
a
Volumes and clearances are scaled to free-drug concentrations.