Table 2.
Summary of pharmacokinetic parameters after a single dose of vismodegib 150 mg (a) and after 14 days of vismodegib 150 mg daily (b). Exposure parameters (Ctrough, Cmax and AUC) are reported as geometric mean (CV%), while Tmax and Tlag are reported as mean ± SD.
| a. | ||||||
|---|---|---|---|---|---|---|
| Fasting (FO) (n=22) |
High fat (HF) (n=20) |
Low fat (LF) (n=18) |
p- value |
Ratio of geometric means (90% CI) |
||
| Cmax (ng/ml) | 3244 (55) | 5666 (45) | 3511 (40) | HF/FO | 0.003 | 1.75 (1.30, 2.34) |
| LF/FO | 0.65 | 1.08 (0.81, 1.44) | ||||
| AUC0–168 (ng*h/mL) | 416635 (56) | 723822 (54) | 466566 (38) | HF/FO | 0.008 | 1.74 (1.25, 2.42) |
| LF/FO | 0.51 | 1.12 (0.84, 1.49) | ||||
| Tmax (hours) | 57 ± 62 | 44 ± 48 | 62 ± 57 | HF/FO | 0.83 | -- |
| LF/FO | 0.57 | -- | ||||
| Tlag (hours) | 0.11 ± 0.17 | 0.50 ± 0.29 | 0.58 ± 0.45 | HF/FO | 0.0001 | -- |
| LF/FO | 0.0001 | -- | ||||
| b. | ||||
|---|---|---|---|---|
| Fasting (n=25) | Fed (n=27) | p-value | Ratio of geometric means (90% CI) |
|
| Ctrough (ng/ml) | 10493 (37) | 12171 (35) | 0.17 | 1.16 (0.97, 1.38) |
| Cmax (ng/ml) | 11449 (37) | 12950 (34) | 0.25 | 1.13 (0.95, 1.35) |
| AUC0–24 (ng*h/mL) | 238740 (40)a | 290896 (35)b | 0.096 | 1.22 (1.00, 1.48) |
| Tmax (hours) | 6.7 ± 9.1 | 10.2 ± 10.3 | 0.27 | -- |
a
n = 22;
b
n = 25