Table 2.
Population parameter estimates of the final PK model in comparison to the model of Yu et al.24
| Our study | Yu et al.24 | ||||||
|---|---|---|---|---|---|---|---|
| Parameter | Unit | Estimate (RSE, %) | IIV% (RSE, %) | Bootstrap mean | Bootstrap 90% CI | Estimate (RSE, %) | IIV% (RSE, %) |
| Sunitinib (parent drug) | |||||||
| ka | 1/h | 0.133 (34.6) | ‐ | 0.149 | 0.01–0.25 | 0.34 (10.8) | ‐ |
| CL | L/h | 33.9 (6.0) | 30.3 (29.0) | 33.92 | 30.76–37.53 | 35.7 (5.7) | 33.9 (12.0) |
| V1 | L | 1820 (6.6) | 25.3 (30.3) | 1812.1 | 1607.8–1812.2 | 1360 (6.0) | 32.4 (10.6) |
| V2 | L | 588a | ‐ | 588a | ‐ | ‐ | ‐ |
| Q | L/h | 0.371 (18.9) | ‐ | 0.373 | 0.263–0.494 | ‐ | ‐ |
| QH | L/h | 80a | ‐ | 80a | ‐ | 80a | ‐ |
| Residual error (proportional) | ‐ | −0.367 (14.1) | ‐ | −0.361 | −0.450 to −0.283 | 0.06 (13.5) | |
| SU12662 (metabolite) | |||||||
| CLm | L/h | 16.5 (5.4) | ‐ | 16.5 | 15.0–17.9 | 17.1 (7.4) | 42.1 (7.0) |
| V1,m | L | 730 (14.1) | 42.9 (54.8) | 713.6 | 545.9–872.9 | 635 (13.1) | 57.9 (8.8) |
| V2,m | L | 592 (13.2) | ‐ | 604.9 | 481.0–737.4 | 388 (14.9) | ‐ |
| Qm | L/h | 2.75 (24.6) | ‐ | 2.90 | 1.96–4.27 | 20.1 (32.6) | ‐ |
| fm | ‐ | 0.21a | 34.6 (20.5) | 0.21a | ‐ | 0.21a | ‐ |
| Residual error (proportional) | ‐ | −0.281 (10.8) | ‐ | −0.276 | −0.326 to −0.229 | 0.03 (14.1) | ‐ |
| Correlations | |||||||
| ρ (CL,V1) | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| ρ (CL, CLm) | ‐ | ‐ | ‐ | ‐ | ‐ | 0.53 | ‐ |
| ρ (CL, V 1,m) | ‐ | −0.0607 (48.3) | ‐ | −0.0685 | −0.127 to −0.019 | ‐ | ‐ |
| ρ (V1, V1,m) | ‐ | 0.0481 (51.8) | ‐ | 0.0534 | 0.0091 to −0.0996 | 0.48 | ‐ |
| ρ (CLm, V1,m) | ‐ | ‐ | ‐ | ‐ | 0.45 | ‐ | |
| ρ (CL, fm) | ‐ | −0.0425 (40.8) | ‐ | −0.0392 | −0.0671 to −0.0130 | ‐ | ‐ |
| ρ (V1, fm) | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| ρ (fm, V1,m) | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
CI, confidence interval; CL, clearance of sunitinib; CLm, clearance of the metabolite SU12262; fm, fraction metabolized to SU12662; IIV, interindividual variability; ka, absorption rate constant; prop, proportional error model; PK, pharmacokinetic; Q, intercompartmental clearance of sunitinib; QH, liver blood flow; Qm, intercompartmental clearance of the metabolite SU12662; ρ, correlation coefficient; RSE, relative standard error; V1, volume of the central compartment of sunitinib; V1,m, volume of the central compartment of the metabolite SU12662; V2, volume of the peripheral compartment of sunitinib; V2,m, volume of the peripheral compartment of the metabolite SU12662.
Parameter fixed to literature value.