Table 2.
Estimated population means and between-subject variabilities for the different elimination models based on NONMEM
| Parametera (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 | +76.9 | +13.8 | 0 | −14.3 |
| CLR (liters/h) | 8.46 (39) | 4.42 (47) | 4.96 (42) | |
| VmaxR (mg/h) | 1,980 (33) | 219 (84) | 134 (70) | |
| KmR (mg/liter) | 199 (65) | 36.1 (112) | 24.0 (107) | |
| CLNR (liters/h) | 3.40 (30) | 5.49 (18) | 5.44 (18) | |
| VmaxNR (mg/h) | 3,350 (122) | |||
| KmNR (mg/liter) | 456 (142) | |||
| Vss (liters) | 12.0 | 12.8 | 12.6 | 13.4 |
| V1 (liters) | 6.42 (18) | 6.20 (18) | 6.32 (18) | 6.32 (20) |
| V2 (liters) | 3.63 (40) | 4.02 (48) | 3.59 (48) | 3.52 (45) |
| V3 (liters) | 1.92 (31) | 2.61 (16) | 2.69 (15) | 3.58 (7) |
| CLicshallow (liters/h) | 14.0 | 18.3 | 15.2 | 16.4 |
| CLicdeep (liters/h) | 0.623 | 1.67 | 1.65 | 2.55 |
| TK0 (fixed; min) | 5 | 5 | 5 | 5 |
| CVC (%) | 13.1 | 12.8 | 12.8 | 12.4 |
| SDC (mg/liter) | 0.31 | 0.27 | 0.26 | 0.28 |
| CVAU (%) | 39.0 | 25.5 | 24.7 | 22.5 |
| SDAU (mg) | 1.44 | 4.21 | 4.17 | 4.30 |
Estimated population means (coefficients of variation for between-subject variability) for different elimination models from NONMEM (using the FOCE+I algorithm), including between-subject variability and a full covariance matrix for all parameters except for CLicshallow and CLicdeep. Abbreviations: CLR, first-order renal clearance; VmaxR, maximum rate of elimination for mixed-order renal elimination; KmR, Michaelis-Menten constant for mixed-order renal elimination; CLNR, nonrenal clearance; VmaxNR, maximum rate of elimination for mixed-order nonrenal elimination; KmNR, Michaelis-Menten constant for mixed-order nonrenal elimination; Vss, volume of distribution at steady state; V1, volume of distribution for central compartment; V2 volume of distribution for the shallow peripheral compartment; V3, volume of distribution for the deep peripheral compartment; CLicshallow, intercompartmental clearance between the central and the shallow peripheral compartments; CLicdeep, intercompartmental clearance between the central and the deep peripheral compartments; TK0, duration of zero-order input (not estimated); CVC, proportional residual error component for the plasma drug concentrations; SDC, additive residual error component for the plasma drug concentrations; CVAU, proportional residual error component for the amounts of drug excreted in urine; SDAU, additive residual error component for the amounts of drug excreted in urine.
Objective function differences were calculated based on the −2× log likelihood.