Table 1.
PK parameters (CV %) for vismodegib following single-dose (day 1 or 5) and multiple-dose (day 7 or 11, steady state) administration of oral vismodegib (150 mg QD)
| Arm A Vismodegib (n = 22) |
Arm B Vismodegib + rabeprazole (n = 24) |
Arm C Vismodegib + itraconazole (n = 22) |
Arm D Vismodegib + fluconazole (n = 22) |
|
|---|---|---|---|---|
| Single-dose | ||||
| Collection day | 1 | 5 | 1 | 1 |
| AUC0–24h (µmol h/L) | 140 (60.0) | 80.7 (45.6) | 111 (44.3) | 159 (35.2) |
| C max (µmol/L) | 7.00 (55.8) | 4.56 (36.9) | 5.65 (37.4) | 8.01 (33.2) |
| t amax (h) | 6.00 (2.0, 24.0) | 23.9 (2.0, 24.0) | 23.9 (2.0, 23.9) | 23.9 (1.0, 24.0) |
| t a,bss (h) | 95.9 (48.0, 120.0) | 95.9 (71.9, 144.0) | NC | NC |
| Multiple-dose | ||||
| Collection day | 7 | 11 | 7 | 7 |
| AUC0–24h (µmol h/L) | 402 (33.3) | 346 (25.5) | 388 (20.8) | 526 (22.4) |
| C ss,ave (µmol/L) | 16.7 (33.4) | 14.4 (25.4) | 16.2 (20.8) | 21.9 (22.4) |
| C ss,ave,u (µmol/L) | 0.150 (50.2) | 0.101 (32.8) | 0.147 (39.9) | 0.236 (29.7) |
Geometric mean (CV %) data are presented unless indicated
CV % coefficient of variation, NC not calculated, PK pharmacokinetic, QD once daily
aMedian (min, max) presented for t max and t ss
b t ss estimated after continuous QD dosing (AUC0–24h, C max, and t max estimated after the first dose)