Table 4.
Pharmacokinetics of regorafenib and its metabolites after single dosing (Cycle 0 Day 1) and multiple dosing (Cycle 1 Day 21)
| Regorafenib | M2 | M5 | |
|---|---|---|---|
| Cycle 0, day 1 | N = 15 | ||
| C max (μg/L) | 1,373.6 (108.0) | 273.3 (388.9) | 31.1 (167.3)a |
| AUC (μg.h/L) | 34,559.8 (84.2) | 7,820.6 (301.2) | 3,441.8 (112.0)a |
| AUC0–24 (μg.h/L) | 16,357.6 (86.1) | 3,697.2 (340.5) | 380.5/164.2 (112.0)a |
| t 1/2 (h) | 27.4 (29.9) | 24.8 (27.7) | 60.8 (78.2)a |
| t max (h) | 4.0 (1.9–8.1) | 4.3 (2.8–24.0) | 24.0 (2.8–71.3)a |
| Cycle 1, day 21 | N = 12 | ||
| C max (μg/L) | 2,522.2 (77.0) | 1,040.3 (213.7) | 515.1 (413.9) |
| AUC0–24 (μg.h/L) | 33,042.8 (68.5) | 15,623.0 (212.5) | 7,118.4 (458.6) |
| t 1/2 (h) | 30.4 (26.2) | 29.5 (24.1) | 57.5 (33.7) |
| t max (h) | 3.6 (0.6–47.9) | 4.3 (0.6–47.9) | 35.6 (0.6–73.2) |
| Accumulation ratio | |||
| RAAUC | 2.1 (64.6) | 5.2 (136.9) | 37.3 (109.3)b |
| RA C max | 2.0 (78.3) | 4.8 (131.5) | 36.0 (80.5)b |
Data are geometric means (% coefficient of variance), except for t max, where data are median (range)
AUC area under the concentration–time curve; AUC 0–24 AUC from 0 to 24 h; C max maximum concentration; M2 regorafenib N-oxide metabolite; M5 regorafenib N-oxide/N-desmethyl metabolite; R A AUC accumulation ratio calculated from the AUCT (expected dosing interval) obtained after multiple dosing and AUCT after single dosing; R A C max accumulation ratio calculated from C max after multiple dosing and C max after single dosing; t 1/2 terminal half life; t max time to maximum concentration
a n = 13
b n = 10