TABLE 1.
Base structural and final population PK model for oritavancin
| Parameter | Base structural population PK modela
|
Final population PK modelb
|
||||||
|---|---|---|---|---|---|---|---|---|
| Population mean
|
Magnitude of interindividual variability (%CV)
|
Population mean
|
Magnitude of interindividual variability (%CV)
|
|||||
| Final estimate | %SEM | Final estimate | %SEM | Final estimate | %SEM | Final estimate | %SEM | |
| CL (liter/h) | 0.453 | 1.83 | 42.2 | 0.0000413 | 0.456 | 33.7 | 8.71 | |
| Vc (liter) | 5.89 | 1.72 | 37.1 | 0.0000805 | 5.88 | 35.2 | 8.96 | |
| Q2 (liter/h) | 0.846 | 2.64 | 57.5 | 0.0601 | 0.872 | 3.68 | 60.2 | 11.3 |
| V2 (liter) | 14.2 | 1.45 | 31.7 | 0.0970 | 14.8 | 5.63 | 86.9 | 11.3 |
| Q3 (liter/h) | 0.318 | 3.51 | 80.2 | 0.000109 | 0.259 | 4.78 | 76.5 | 8.86 |
| V3 (liter) | 99.7 | 2.52 | 57.8 | 0.0153 | 90.0 | 5.61 | 79.5 | 10.7 |
| CL intercept (liter/h) | 0.0374 | 2.04 | ||||||
| CL WTKG slope (liter/h/kg) | 0.00164 | 26.9 | ||||||
| CL shift, phase 2/3 patients | 1.30 | 10.0 | ||||||
| Vc intercept (liter) | 5.56 | 2.07 | ||||||
| Vc BSA slope (liter/m2) | 1.85 | 16.6 | ||||||
| Vc age slope (liter/yr) | −0.0354 | 16.6 | ||||||
| SDin | 0.220 | |||||||
| SDsl | 0.250 | 1.11 | ||||||
| SDin, phase 1 subjects | 0.150 | |||||||
| SDsl, phase 1 subjects | 0.146 | 1.59 | ||||||
| SDin, phase 2/3 patients | 0.220 | |||||||
| SDsl, phase 2/3 patients | 0.304 | 1.80 | ||||||
a
Minimum value of the objective function, 11,501.
b
Minimum value of the objective function, 10,568. Final population mean CL = {0.374 + [0.00164·(WTKG − 80)·(1 − WTKGc)]·1.30(1 − phase 1)}. WTKGc is an indicator variable set to 1 if WTKG is ≤80 and set to 0 if WTKG is >80, and phase 1 is an indicator variable set to 1 for phase 1 subjects and set to 0 for phase 2 or 3 patients. Final population mean Vc = 5.56 + [1.85·(BSA − 1.73)] − [0.0354·(age − 48)].