Table 2.
Plasma pharmacokinetic parameters of venetoclax administered to healthy non-childbearing adult females in bioavailability phase I studies
| Study regimen description | N | Fed state | Pharmacokinetic parameters | ||||
|---|---|---|---|---|---|---|---|
| Cmax, µg/mL | Tmaxa, h | t½b, h | AUCt, µg⋅h/mL | AUC∞, µg⋅h/mL | |||
| Study 1: 100 mg single dose administered as tablets of varying strengths under low-fat conditions | |||||||
| 1 × 100 mg tablet | 37 | Fed | 0.552 (0.590, 34) | 6 (4.0–8.0) | 13.6 (2.04) | 6.44 (7.07, 46) | 6.59 (7.26, 48) |
| 2 × 50 mg tablets | 38 | Fed | 0.522 (0.559, 35) | 6 (4.0–10.0) | 13.6 (3.06) | 5.82 (6.51, 48) | 5.96 (6.71, 51) |
| 10 × 10 mg tablets | 39 | Fed | 0.515 (0.550, 33) | 6 (4.0–8.0) | 13.6 (3.58) | 5.75 (6.37, 46) | 5.9 (6.57, 49) |
| Study 2: 100 mg single-dose tablet or oral powder under fasted or high-fat conditions | |||||||
| 1 × 100 mg tablet | 16 | Fed | 0.863 (0.913, 32) | 6 (4.0–10) | 14.7 (2.76) | 10.5 (11.4, 42) | 10.8 (11.8, 44) |
| 7.2% oral powder | 16 | Fed | 0.74 (0.780, 34) | 6 (4.0–8.0) | 13.4 (2.83) | 11.7 (12.6, 40) | 12 (13.0, 42) |
| 7.2% oral powder | 8 | Fasted | 0.283 (0.297, 33) | 4 (4.0–4.0) | 14.3 (4.87) | 3.5 (3.69, 34) | 3.63 (3.83, 34) |
| 0.72% oral powder | 16 | Fed | 0.69 (0.711, 26) | 6 (4.0–10) | 13 (1.86) | 11.3 (12.2, 41) | 11.6 (12.6, 43) |
| 0.72% oral powder | 8 | Fasted | 0.291 (0.310, 38) | 4 (4.0–6.0) | 16.2 (4.93) | 4.2 (4.71, 51) | 4.4 (4.97, 54) |
| Study 3: 100 mg single-dose oral powder in four vehicles under moderate-fat conditions | |||||||
| 7.2% oral powder in water | 10 | Fed | 0.637 (0.649, 20) | 6 (4.0–6.0) | 14.3 (2.28) | 7.11 (7.33, 26) | 7.24 (7.46, 26) |
| 7.2% oral powder in apple juice | 11 | Fed | 0.642 (0.671, 31) | 4 (4.0–6.0) | 13.6 (3.08) | 6.69 (7.16, 42) | 6.80 (7.29, 42) |
| 7.2% oral powder in apple sauce | 12 | Fed | 0.648 (0.669, 31) | 4 (4.0–6.0) | 14.7 (1.42) | 6.74 (7.14, 44) | 6.85 (7.26, 44) |
| 7.2% oral powder in yogurt | 11 | Fed | 0.623 (0.665, 35) | 4 (4.0–6.0) | 14.1 (2.72) | 6.93 (7.59, 43) | 7.05 (7.73, 44) |
| 0.72% oral powder in water | 12 | Fed | 0.692 (0.717, 29) | 6 (4.0–6.0) | 14.3 (1.92) | 8.60 (9.23, 40) | 8.77 (9.42, 40) |
| 0.72% oral powder in apple juice | 12 | Fed | 0.717 (0.738, 26) | 6 (4.0–6.0) | 14.2 (1.58) | 8.56 (8.97, 33) | 8.73 (9.16, 33) |
| 0.72% oral powder in apple sauce | 12 | Fed | 0.784 (0.793, 16) | 6 4.0–6.0) | 14.3 (1.59) | 8.96 (9.30, 29) | 9.15 (9.50, 29) |
| 0.72% oral powder in yogurt | 12 | Fed | 0.735 (0.766, 28) | 6 (4.0–6.0) | 15.3 (1.97) | 8.86 (9.50, 38) | 9.07 (9.74, 39) |
Note: Parameters are presented as geometric mean [mean (CV%)] unless otherwise noted. Low-fat meals consisted of ≤ 700 Kcal with ≤ 20% of the total caloric intake from fat; moderate-fat (standardized diet) meals consisted of ~ 700 Kcal with ~ 30% of caloric intake from fat; and high-fat meals consisted of 800–1000 Kcal with ~ 50% of the caloric intake from fat
AUC∞ area under the plasma concentration–time curve from time zero to infinite time, AUCt area under the plasma concentration–time curve from time zero to time of the last measurable concentration, Cmax maximum observed plasma concentration, CV coefficient of variation, t½ terminal phase elimination half-life, Tmax time to reach maximum observed plasma concentration
aMedian (minimum–maximum)
bHarmonic mean (pseudo-standard deviation)