Table 3.
Summary of final model pharmacokinetic parameters for sunitinib and SU012662
| Parameter | Sunitinib | SU012662 | ||
|---|---|---|---|---|
| Results, mean (RSE %) | Bootstrap, median (95% CI) | Results, mean (RSE %) | Bootstrap, median (95% CI) | |
| CL/F (θ1), l/h | 24.0 (5.8) | 23.8 (15.4–26.7) | 11.1 (6.9) | 11.1 (9.35–12.6) |
| Vc/F (θ2), l | 1030 (9.8) | 1006 (845–1164) | 1060 (14) | 975 (543–1193) |
| ka (θ3), h–1 | 0.37 (28.3) | 0.35 (0.23–0.62) | 0.28 (36.7) | 0.26 (0.15–0.37) |
| tlag (θ4), h | 0.76 (3.6) | 0.75 (0.57–0.88) | 0.64 (26.3) | 0.65 (0.44–0.76) |
| Vp/F (θ5), l | 81.3 (22.9) | 95.4 (64.3–425,327) | 63.1 (141) | 113 (0.63–4902) |
| Q/F (θ6), 1/h | 0.39 (79.6) | 0.46 (0.26–11.4) | 6.7 (319) | 9.75 (0.09–50,575) |
| BSA on CL/F (θ9) | 0.73 (25.6) | 0.75 (0.41–1.34) | 0.87 (26) | 0.87 (0.48–1.27) |
| BSA on Vc/F (θ8) | 1.46 (19.9) | 1.47 (0.99–1.83) | 1.61 (20) | 1.82 (1.23–3.52) |
| ω (CL/F), % | 33 (35.4) | 32.7 (26.5–51.2) | 44 (19.8) | 42.5 (30.9–55.2) |
| ω (Vc/F), % | 25.3 (45.2) | 21.8 (0.25–40.8) | 42 (37.6) | 43.7 (27.2–64.4) |
| ω (ka), % | 103.4 (41.5) | 100.6 (67.2–148) | 95.7 (42.4) | 90 (52.3–122) |
| σ (θ7), % | 32.2 (2.3) | 31.7 (26–38) | 26 (3.24) | 25.8 (22–31) |
BSA body surface area, CI confidence interval, CL/F apparent clearance, ka first-order absorption rate constant, tlag lag time; Q/F apparent inter-compartmental clearance, RSE relative standard error, Vc/F central compartment apparent volume of distribution, Vp/F peripheral compartment apparent volume of distribution, σ residual variability, ω interindividual variability