TABLE 1.
Development of structural model for pharmacokinetics of tafenoquine
| Model | Parameterizationd | ΔOFVa |
|---|---|---|
| 1 | CL/F = θ1; V/F = θ2; Ka = θ3 | |
| 2 | CL/F = θ1·(1 + θ4·age/25.4); V/F = θ2; Ka = θ3 | −2 |
| 3 | CL/F = θ1; V/F = θ2·(1 + θ4·age/25.4); Ka = θ3 | −9b |
| 4 | CL/F = θ1·(1 + θ4·CLCR/121); V/F = θ2; Ka = θ3 | −4 |
| 5 | CL/F = θ1·PHOS + θ4·(1 − PHOS); V/F = θ2; Ka = θ3 | 0 |
| 6 | CL/F = θ1; V/F = θ2·PHOS + θ4·(1 − PHOS); Ka = θ3 | −1b |
| 7 | CL/F = θ1·sex + θ4·(1 − sex); V/F = θ2; Ka = θ3 | −3b |
| 8 | CL/F = θ1; V/F = θ2·sex + θ4·(1 − sex); Ka = θ3 | −12 |
| 9c | CL/F = θ1·(1 + θ4·WT/80.9); V/F = θ2·(1 + θ5·WT/80.9); Ka = θ3 | −39 |
| 10 | CL/F = θ1·(WT/70)0.75; V/F = θ2·(WT/70)1.0; Ka = θ3 | +37b |
a
ΔOFV, change in OFV from that of model 1 (OFV = 22,177).
b
Rounding errors occurred during fitting.
c
Final model.
d
WT/80.9, body weight (kg) centered on average weight (80.9 kg); age/25.4, age (years) centered on average age (25.4 years); CLCR/121, CLCR (ml/min) centered on average CLCR (121 ml/min); PHOS, phospholipidosis (tested in 77 subjects; 1 = phospholipidosis present, 0 = phospholipidosis not present); sex, male = 0 and female = 1.