Table 4.
Summary of sorafenib and sorafenib N-oxide pharmacokinetic parameters (Supplementary Figure)
| Pharmacokinetic Parametersa | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Dose Level |
Dose (mg) |
Tmax (h) |
Cmax (µg/mL) |
AUC0–8h (µg*h/mL) |
Day 2 Cmin (µg/mL) |
Day 3 Cmin (µg/mL) |
Day 8 Cmin (µg/mL) |
Day 15 Cmin (µg/mL) |
Css,min (µg/mL) |
Day 29 C (µg/mL) |
| Sorafenib | ||||||||||
| 1 | 400 | 2.3 (2.1–8.0, 3) |
1.93±2.25 (3) |
9.1±8.6 (3) |
0.49, 1.17 (2) |
1.79±1.60 (3) |
3.07±1.79 (3) |
2.06±1.50 (3) |
2.57±1.57 (3) |
0.19 (1) |
| 2 | 400 | 4.0 (2.0–4.1, 9) |
4.37±2.64 (9) |
20.8±12.9 (9) |
3.26±2.75 (5) |
5.08±3.22 (6) |
4.75±4.82 (4) |
7.13±6.88 (3) |
4.79±4. 90 (5) |
0.27±0.30 (4) |
| 1 and 2 | 400 | 3.1 (2.0–8.0, 12) |
3.76±2.68 (12) |
17.9±12.8 (12) |
2.57±2.55 (7) |
3.98±3.14 (9) |
4.03±3.68 (7) |
4.60±5.25 (6) |
3.95±3.97 (8) |
N.C. |
| 3 | 600 | 8.0 (4.0–8.0, 3) |
3.10±1.07 (3) |
12.6±4.1 (3) |
2.49 (1) |
N.R. | 7.79 (1) |
3.65 (1) |
5.72 (1) |
N.R. |
| Sorafenib N-oxide | ||||||||||
| 1 | 400 | 8.0 (1) |
0.04 (1) |
0.2 (1) |
0.01 (1) |
0.17 (1) |
0.18±0.17 (3) |
0.09±0.11 (3) |
0.14±0.14 (3) |
N.R. |
| 2 | 400 | 4.0 (1.1–8.0, 8) |
0.26±0.19 (8) |
1.3±1.0 (8) |
0.37±0.43 (4) |
0.560.58 (6) |
0.51±0.71 (4) |
0.54±0.69 (3) |
0.43±0.57 (5) |
0.09, 0.20 (2) |
| 1 and 2 | 400 | 4.0 (1.1–8.0, 9) |
0.23±0.19 (9) |
1.2±1.0 (9) |
0.30±0.41 (5) |
0.50±0.55 (7) |
0.37±0.54 (7) |
0.32±0.50 (6) |
0.32±0.46 (8) |
N.C. |
| 3 | 600 | 8.0 (4.0–8.0, 3) |
0.21±0.26 (3) |
0.8±1.0 (3) |
0.23 (1) |
N.R. | 0.53 (1) |
0.47 (1) |
0.50 (1) |
N.R. |
Values are reported as the mean ± standard deviation (n). For Tmax, values are reported as median (range, n). When n≤2, individual values are reported. One µg/mL of sorafenib or sorafenib N-oxide is equivalent to 2.15 and 2.08 µM, respectively.
Css,min is an average of day 8 and 15 Cmin (or either day if a sample was not obtained in a patient)
For Day 29 concentrations, the average for dose level 1 and 2 is not calculated (N.C.) since the dosing schedule is different
Abbreviations: AUC, area under the concentration-time curve; Cmax, maximal plasma concentration; Css,min, minimal plasma concentration; Css,min, minimal plasma concentration at steady-state (average of day 8 and 15 Cmin); N.R., not reported; Tmax, time of the maximal plasma concentration