Table 3.
Pharmacokinetic and covariate parameter estimates of the base and final models
| Parameter descriptions | Base PK model | Final PK model | ||||
|---|---|---|---|---|---|---|
| Population estimates (%SEE) | Interpatient variability (%SEE) | Population estimates (%SEE) | Interpatient variability (%SEE) | Bootstrap results (95% CI) | Bootstrap results of interpatient variability (95% CI) | |
| Structural model | ||||||
| Clearance, CL (L/h) | 0.0241 (4.02) | 38.2% (15.7) | 0.0233 (3.67) | 33.3% (12.9) | 0.0233 (0.0215–0.0253) | 32.8% (27.7–38.0) |
| Central volume of distribution, V 1 (L) | 4.19 (4.32) | 22.2% (18.8) | 4.16 (1.79) | 15.6% (30.1) | 4.15 (3.99–4.31) | 15.4% (11.4–19.1) |
| Peripheral volume of distribution, V 2 (L) | 3.58 (20.1) | – | 3.58 (13.2) | – | 3.66 (2.69–4.90) | |
| Intercompartmental clearance, Q (L/h) | 0.0316 (25.6) | – | 0.0315 (25.8) | – | 0.0335 (0.0196–0.0524) | |
| Residual error model | ||||||
| Additive (µg/mL) | 9.78 (56.2) | 10.1 (15.5) | 11.4 (3.56–31.5) | |||
| Proportional | 22.6% (24.8) | 22.5% (18.1) | 22.2 (16.5–27.2) | |||
| Covariate model | ||||||
| WTECL a | – | 0.431 (10.2) | 0.433 (0.216–0.654) | |||
| b | – | 0.610 (12.9) | 0.611 (0.476–0.760) | |||
| TUMRCL a | – | 0.00158 (25.8) | 0.00159 (0.000817–0.00252) | |||
SEE standard error of the estimate, CI confidence interval, PK pharmacokinetic, TUMR CL tumor size effect on clearance, WTE CL body weight effect on clearance, WTE V1 body weight effect on central volume of distribution
aCLind = CL × (WTE/median(WTE))^WTECL × (1 + TUMRCL × (TUMR − median(TUMR))
b