Table 3.
Summary of pharmacokinetic parameters of adavosertib following co-administration of cocktail (pharmacokinetic analysis set)
| AUC0–12, nM·h | Cmax, nM | Cmin, nM | Cavg, nM | tmax, h | CLss/F, L/h | FI, % | |
|---|---|---|---|---|---|---|---|
| Geometric mean, n = 16 (N = 22) | 12,170 | 1437 | 567 | 1018 | ND | ND | ND |
| CV, % | 31.9 | 29.0 | 36.7 | 32.2 | ND | ND | ND |
| Arithmetic mean (SD) (n = 16, N = 22) |
12,720 (3796) |
1490 (398) |
602 (219) |
1065 (319) |
ND (ND) |
38.0 (12.11) |
85.7 (24.3) |
| Median (minimum, maximum) |
11,970 (6950, 18,200) |
1415 (853, 2120) |
563 (344, 1050) |
991 (580, 1540) |
3.0 (0.75, 6.00) |
36.9 (24.3, 63.5) |
79.8 (54.3, 135.8) |
Treatment: adavosertib + cocktail: caffeine (200 mg tablet), omeprazole (20 mg capsule), and midazolam (1 mL of 2 mg/mL syrup formulation) on day 3. CV calculated as 100 x √[exp(s2)–1], where s is the SD of the data on a log scale. AUC0–12 area under the plasma concentration–time curve from time zero to 12 h, Cavg apparent average plasma concentration over a dosing interval, CLss/F apparent clearance at steady state, Cmax maximum plasma drug concentration, Cmin minimum plasma drug concentration, CV coefficient of variance, FI fluctuation index over a dosing interval, ND not determined, SD standard deviation, tmax time to reach maximum plasma concentration