Table 3.
Estimated population means and between-subject variabilities for the different elimination models based on S-ADAPTa
| Parameter (units) | Type of elimination model or estimated population mean (% BSV CV) |
|||
|---|---|---|---|---|
| Model 1 | Model 2 | Model 3 | Model 4 | |
| Renal elimination | First order | Mixed order | Parallel first order and mixed order | Parallel first order and mixed order |
| Nonrenal elimination | First order | First order | First order | Mixed order |
| Δ objective functionb | +69.6 | +10.6 | 0 | −4.5 |
| CLR (liters/h) | 8.37 (41) | 4.70 (39) | 4.56 (41) | |
| VmaxR (mg/h) | 2,327 (40) | 234 (52) | 254 (60) | |
| KmR (mg/liter) | 239 (76) | 46.0 (108) | 48.3 (122) | |
| CLNR (liters/h) | 3.24 (35) | 5.29 (19) | 5.26 (19) | |
| VmaxNR (mg/h) | 3,655 (79) | |||
| KmNR (mg/liter) | 560 (88) | |||
| Vss (liters) | 11.7 | 13.0 | 12.7 | 13.3 |
| V1 (liters) | 6.35 (19) | 6.20 (19) | 6.35 (19) | 6.35 (20) |
| V2 (liters) | 3.42 (45) | 4.28 (48) | 3.79 (50) | 4.04 (44) |
| V3 (liters) | 1.96 (32) | 2.50 (26) | 2.55 (26) | 2.91 (16) |
| CLicshallowc (liters/h) | 14.4 (15) | 17.3 (15) | 14.8 (15) | 15.6 (15) |
| CLicdeepc (liters/h) | 0.695 (15) | 1.17 (15) | 1.19 (15) | 1.58 (15) |
| TK0 (fixed; min) | 5 | 5 | 5 | 5 |
| CVC (%) | 11.9 | 12.0 | 12.0 | 11.8 |
| SDC (mg/liter) | 0.22 | 0.18 | 0.17 | 0.19 |
| CVAU (%) | 34.2 | 22.6 | 20.7 | 19.0 |
| SDAU (mg) | 1.19 | 2.61 | 2.87 | 3.24 |
a
Estimated population means (coefficients of variation for between-subject variability) for different elimination models from S-ADAPT (MC-PEM algorithm), including estimated between-subject variability and a full covariance matrix for all parameters except CLicshallow and CLicdeep. For parameter explanations, see footnote a of Table 2.
b
Objective function differences were calculated based on the −2× log likelihood.
c
The BSV CLicshallow and CLicdeep values were fixed to 15% not estimated.