Table 2.
Population PK parameters
| Parameter estimate (bootstrap 5th, 95th percentiles) | ||
|---|---|---|
| Parameter name | BLQ data included | BLQ data excluded |
| PK parameter (unit) | ||
| V2 (L) | 2.74 (2.61, 2.97) | 2.60 (2.46, 2.79) |
| ke (1/d) | 0.0459 (0.0403, 0.0503) | 0.0488 (0.0422, 0.0566) |
| k23 (1/d) | 0.0652 (0.0431, 0.0917) | 0.104 (0.0755, 0.150) |
| k32 (1/d) | 0.129 (0.101, 0.166) | 0.173 (0.133, 0.234) |
| ka (1/d) | 0.254 (0.226, 0.315) | 0.261 (0.223, 0.303) |
| Vm (mg/L/d) | 0.968 (0.836, 1.09) | 1.06 (0.946, 1.20) |
| Km (mg/L) | 0.01 (fixed) | 0.01 (fixed) |
| F (unitless) | 0.607 (0.537, 0.665) | 0.623 (0.572, 0.678) |
| Covariate influence | ||
| V2 ∼ weight | 0.705 (0.576, 0.840) | 0.737 (0.588, 0.914) |
| Inter‐individual variability | ||
| ω2 (V2)a | 0.0225 (0.0152, 0.0285) | 0.0295 (0.0189, 0.0419) |
| ω2 (ke) | 0.131 (0.0738, 0.191) | 0.131 (0.0733, 0.181) |
| ω2 (ka) | 0.251 (0.187, 0.345) | 0.230 (0.169, 0.293) |
| ω2 (Vm) | 0.0428 (0.0215, 0.0663) | 0.0379 (0.0120, 0.0705) |
| Residual variability (unit) | ||
| σ2 proportional (CV%) | 24.2 (22.1, 27.0) | 18.2 (15.1, 21.1) |
| σ2 additive (mg/L) | 0.03 (fixed) | 0.871 (0.579, 1.32) |
| Derived parametersb | ||
| CL (L/d)b,c | 0.126 | 0.127 |
| Q (L/d) | 0.179 | 0.270 |
| V3 (L) | 1.38 | 1.56 |
a
aV2 is adjusted for body weight. bLinear clearance calculated as V2·ke. cAs the kinetics are substantially nonlinear, the beta half‐life and linear clearance cannot be used to calculate time to the LLOQ concentration or another concentration of interest. No attempts should be made to do this to predict when patients reach clinically insignificant concentrations. Instead, model‐based predictions should be used, which are proved to be precise.