Table 3.
Veliparib plasma pharmacokinetic parameters.
| Day -2 | Day -2 | Day -2 | Day -2 | Day -2 | Day -2 | Day 1 | Day 1 | Day 1 | |
|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||
| Veliparib Dose (mg) |
Cmax (ng/mL) |
Cmax/Dose (ng/mL / mg) |
Tmax (h) |
t½ (h) |
AUC0–8 (µg/mL•h) |
AUC0–121 (µg/mL•h) |
Cmax2 (ng/mL) |
AUC0–121,2 (µg/mL•h) |
Cl/F (L/h) |
| 10 (N=11) | 70.1 (18.4) | 7.01 (1.84) | 1.4 (0.6) | 4.2 (1.2) | 0.29 (0.07) | 0.37 (0.08) | 94.4 (26.0) | 0.53 (0.13) | 25.3 (10.3) |
| 20 (N=16) | 130 (54) | 6.49 (2.71) | 1.8 (1.0) | 5.8 (3.0) | 0.54 (0.15) | 0.68 (0.20) | 213 (79) | 1.16 (0.45) | 17.5 (6.4) |
| 40 (N=3) | 354 (145) | 8.85 (3.62) | 2.0 (1.0) | 4.9 (2.0) | 1.43 (0.47) | 1.76 (0.50) | 325 (109) | 2.41 (1.04) | 18.4 (6.3) |
|
| |||||||||
| Total (N=30) | - | 6.56 (2.69) | 1.7 (0.9) | 5.1 (2.4) | - | - | - | 20.3 (8.6) | |
1
AUC0–12 was calculated based on extrapolating from the 8-h concentration value and the elimination rate. The average extrapolated portion was approximately 20%.
2
The theoretical accumulation index based on observed half-life and 12-h dosing interval was 1.26 (0.25). The observed accumulation index for Cmax and AUC0–12 were 1.51 (0.56), P=0.004 and 1.54 (0.28), P=0.00001 by 2-sided exact Wilcoxon signed ranks test.