Table 2.
Summary of the covariate model-building steps
| Model 1 | Model 2 | Model 3 | Model 4* | |
|---|---|---|---|---|
| Parameter | Base model as two-compartment with lag time | CYP2C19 as covariate for CL/F | CYP3A5 as covariate for CL/F | CYP2C19 and CYP3A5 as covariate for CL/F |
| OFV† | −4001.51 | −4011.83 | −4020.68 | −4032.29 |
| ΔOFV (P-value‡) | – | −10.32 (<0.01) | −19.17 (<0.001) | −11.61 (<0.005) |
| CL/F (l h−1) (%RSE§) | 7.74 (5.57) | 8.66 (11.2) | 11.0 (12.8) | 12.8 (13.9) |
| Vc/F (l) (%RSE) | 19.7 (9.34) | 19.5 (9.59) | 20.3 (7.98) | 20.5 (8.24) |
| Q/F (l h−1) (%RSE) | 5.74 (13.3) | 5.72 (31.1) | 5.65 (19.3) | 5.64 (13.6) |
| Vp/F (l) (%RSE) | 88.8 (28.5) | 90.9 (82.6) | 75.7 (19.4) | 73.1 (21.9) |
| Ka (h−1) (%RSE) | 0.233 (6.31) | 0.232 (5.99) | 0.242 (5.66) | 0.244 (4.80) |
| TLAG (h) (%RSE) | 0.564 (5.05) | 0.564 (5.35) | 0.565 (4.94) | 0.565 (5.12) |
| CL/F, θIMs (%RSE) | – | −0.191 (28.8) | – | −0.147 (33.7) |
| CL/F, θPMs (%RSE) | – | −0.256 (53.5) | – | −0.272 (34.9) |
| CL/F, θ*1/*3 (%RSE) | – | – | −0.183 (70.0) | −0.223 (48.0) |
| CL/F, θ*3/*3 (%RSE) | – | – | −0.384 (22.0) | −0.407 (20.2) |
| ω2CL/F | 0.116 | 0.100 | 0.0862 | 0.0748 |
| ω2Vc/F | 0.480 | 0.479 | 0.482 | 0.481 |
| ω2Q/F | 0.926 | 0.906 | 1.13 | 1.16 |
| ω2Vp/F | 0.639 | 0.640 | 0.707 | 0.688 |
| ωVp/F, CL/F | 0.102 | 0.0964 | 0.0763 | 0.0685 |
| ωQ/F, Vc/F | −0.298 | −0.291 | −0.350 | −0.355 |
| ωVp/F, Q/F | 0.234 | 0.214 | 0.445 | 0.460 |
| σpro | 0.108 | 0.107 | 0.113 | 0.114 |
| σadd (ug ml−1) | 0.0539 | 0.0540 | 0.0517 | 0.0511 |
*
Final model.
†
Objective function value.
‡
Calculated by the log-likelihood ratio test.
§
Percent relative standard error (SE/estimate × 100).