Table 4.
Parameter estimates of the base model, final model, and bootstrap analysis
| Parameter | Base model (RSE %) [shrinkage] | Final model (RSE %) [shrinkage] | Starting dose model (RSE %) [shrinkage] |
|---|---|---|---|
| tlag (h) FIX | 0.41 | 0.41 | 0.41 |
| ka (L/h) | 2.1 (19) | 1.7 (11) | 1.85 (24) |
| CL/F (L/h/70 kg) | 37.0 (6) | 36.6 (12) | 34.5 (6) |
| V1/F (L/70 kg) | 560 (12) | 496 (22) | 540 (12) |
| Q/F (L/h) | 27.4 (16) | 31.7 (19) | 28.5 (12) |
| V2/F (L/70 kg) | 1600 (13) | 1270 (13) | 1660 (17) |
| Allometric scaling on CL | 0.57 (10) | 0.62 (20) | 0.56 (9) |
| Covariate effect on CL | |||
| CYP3A5*1/*1 or *1/*3 | – | 1.4 | 1.5 |
| Hematocrit (L/L) | – | − 0.60 | – |
| Creatinine (µmol/L) | – | − 0.1 | – |
| IIV (%) | |||
|
CL/F V1/F V2/F ka |
47.2 (8) [4] 89.0 (12) [11] 92.1 (15) [20] 172 (10) [23] |
42.1 (10) [5] 99.6 (12) [10] 85.2 (15) [22] 183 (11) [20] |
42.3 (11) [3] 93.0 (12) [8] 89.3 (15) [19] 178 (10) [22] |
| IOV (%) | |||
| CL/F | 20.7 (9) | 20.1 (20) | 20.1 (10) |
| Residual variability | |||
| Additional | |||
|
Immunoassay LC–MS/MS |
0.77 0.94 |
1.27 0.87 |
1.01 0.96 |
| Proportional | |||
|
Immunoassay LC–MS/MS |
0.12 0.23 |
0.11 0.23 |
0.12 0.24 |
CL clearance, CYP cytochrome P450, F bioavailability, IIV inter-individual variability, IOV inter-occasion variability, ka absorption rate constant, LC–MS/MS liquid chromatography–tandem mass spectrometry, Q inter-compartmental clearance, RSE residual standard error, tlag lag time, V1 volume of distribution of the central compartment, V2 volume of distribution of the peripheral compartment