Table 2.
Parameter estimates for pharmacokinetic models for sunitinib and its active metabolite SU12662
| Parameter | Integrated models | Separate models | ||||
|---|---|---|---|---|---|---|
| Current model (n = 70) | Lindauer et al. 17 (n = 12) | Houk et al. 16 (n = 590) | ||||
| Estimate (RSE,%) | IIV, %CV (RSE,%) | Estimate (RSE,%)* | IIV, %CV (RSE,%)* | Estimate (RSE,%) | IIV, %CV (RSE,%) | |
| Sunitinib | ||||||
| RPS | – | – | 1.91(46.8) | – | – | – |
| MTT (h) | – | – | 1.48 (16.6) | – | – | – |
| N | – | – | 1.46 (20.6) | 61 (27) | – | – |
| Ka (h−1) | 0.34 (10.8) | – | 0.54 (10.1) | 26 (44) | 0.195 (6.8) | 81.2 (13) |
| CL (l h−1) | 35.7 (5.7) | 33.9 (12.0) | 32.4 (8.4) | 28 (17) | 37.7 (1.8) | 37.9 (8.8) |
| Vc (l) | 1360 (6.0) | 32.4 (10.6) | 1720 (10.7) | 33 (18) | 1940 (3.8) | 44.7 (13) |
| Qi (l h−1) | – | – | 3.3 (118) | – | 6.37 (18) | – |
| Qh (l h−1) | 80 fix | – | – | – | – | – |
| Vp (l) | – | – | 221 (27.0) | – | 588 (8.7) | – |
| σprop | 0.06 (13.5)† | – | 0.11 (9) | – | 0.147 (9.6) | – |
| 0.01 (10.5)‡ | – | |||||
| σadd (ng ml−1) | 0.07 (65.1) | – | – | – | ||
| SU12662 | ||||||
| Ka (h−1) | – | – | – | – | 0.287 (6.6) | 89.1 (13) |
| CL (l h−1) | 17.1 (7.4) | 42.1 (7.0) | 14.6 (12.5) | 43 (22) | 20.2 (2.3) | 52.2 (8.5) |
| Vc (l) | 635 (13.1) | 57.9 (8.8) | 1410 (15.4) | 47 (18) | 2710 (3.9) | 65.1 (8.7) |
| Qi (l h−1) | 20.1 (32.6) | – | – | – | 27.7 (26) | – |
| Vp (l) | 388 (14.9) | – | – | – | 345 (22) | – |
| σprop | 0.03 (14.1)† | – | 0.11 (10) | – | 0.0913 (7.3) | – |
| 0.01 (12.1)‡ | – | |||||
| σadd (ng ml−1) | 0.36 (22.0) | – | – | – | ||
| Correlations | ||||||
| ρ(CLsunitinib, Vc,sunitinib) | – | – | 0.88 (5.5) | – | – | – |
| ρ(CLsunitinib, CLSU12662) | 0.53 | – | 0.70 (18.7) | – | – | – |
| ρ(CLsunitinib, Vc,SU12662) | – | – | 0.67 (23.6) | – | – | – |
| ρ(Vc,sunitinib, CLSU12662) | – | – | 0.90 (5.1) | – | – | – |
| ρ(Vc,sunitinib, Vc,SU12662) | 0.48 | – | 0.90 (2.0) | – | – | – |
| ρ(CLSU12662, Vc,SU12662) | 0.45 | – | 0.99 (0.3) | – | – | – |
90% confidence intervals (CIs) were originally reported, RSEs were calculated according to 90%CIs.
σprop for study 1.
σprop for study 2 and study 3. ρ, correlation coefficient; σadd, additive residual error; σprop, proportional residual error; CL, clearance; CV, coefficient of variation; IIV, inter-individual variability; Ka, absorption rate constant; MTT, mean transit time; N, number of transit compartments; Qh, hepatic blood flow; Qi, intercompartment clearance; RPS, ratio of pre-systemic to systemic metabolite formation; RSE, relative standard error; Vc, volume of distribution of central compartment; Vp, volume of distribution of peripheral compartment.