Table 2.
Summary of final population pharmacokinetic parameters
| Parameter | Parameter description | Base model estimates (% RSE) | Final model estimate (% RSE) | Bootstrap estimates median (95% CI) |
Final model shrinkage (%) |
|---|---|---|---|---|---|
| exp (θ1*24 | Maximum drug elimination by nonlinear clearance, Vmax (µg/day) | 4.03 (17.0%) | 2.80 (4.13%) | 3.29 (0.77, 10.4) | – |
| exp (θ2) | Michaelis–Menten constant, Km (µg/mL) | 5.63 (15.2%) | 4.45 (8.32%) | 5.58 (0.665, 39.1) | – |
| exp (θ3)*24 | Linear clearance, CL (L/day) | 0.275 (3.53%) | 0.311 (3.68%) | 0.306 (0.261, 0.348) | – |
| θ7 | Influence of body weight on CL | 0.703 (4.00%) | 0.695 (6.46%) | 0.718 (0.518, 0.987) | – |
| θ9 | Influence of albumin on CL | – | − 0.657 (15.2%) | − 0.659 (− 1.03, − 0.312) | – |
| θ10 | Influence of combotherapy/study on CL | – | − 0.200 (23.2%) | − 0.205 (− 0.303, − 0.0849) | – |
| exp (θ4) | Volume of central compartment, Vc (L) | 3.38 (1.42%) | 3.58 (1.64%) | 3.58 (3.46, 3.69) | – |
| θ8 | Influence of body weight on Vc | 0.499 (9.92%) | 0.369 (13.7%) | 0.373 (0.242, 0.491) | – |
| θ11 | Influence of gender on Vc | – | − 0.164 (15.9%) | − 0.165 (− 0.22, − 0.113) | – |
| exp (θ5)*24 | Inter-compartmental clearance, Q (L/day) | 0.953 (13.8%) | 0.952 (12.5%) | 0.928 (0.684, 1.98) | – |
| exp (θ6) | Volume of peripheral compartment, Vp (L) | 2.78 (5.89%) | 2.71 (4.92%) | 2.71 (2.41, 3.09) | – |
| ɷ2Cl, Vc | Covariance between CL and Vc | 0.0172 (34.1%) | 0.0128 (39.8%) | 0.0122 (0.00216, 0.0229) | – |
| Inter-individual variability (% RSE)* | Vmax | 89.9 (10.8%) | 97.4 (6.84%) | 89.8 (58.4, 144) | 44.6% |
| CL | 33.3 (7.24%) | 29.2 (6.50%) | 27.8 (21.0, 32.8) | 13.7% | |
| Vc | 16.4 (6.57%) | 14.9 (7.30%) | 14.6 (12.2, 16.8) | 15.7% | |
| Vp | 59.5 (10.4%) | 60.4 (10.7%) | 59.3 (45.9, 72.7) | 20.5% | |
| δ | Residual variability (%) | 14.5 (4.95%) | 14.6 (5.19%) | 14.5 (13.1, 16.2) | 14.3% |
CI confidence interval, RSE relative standard error
*IIV is expressed as CV%