Table 3.
Pharmacokinetic Profile of Navitoclax
| Dose | Study Daya |
N | Tmax (h) |
Cmax (µg/mL) |
AUC0–24 (µg·hr/mL) |
AUC0-inf (µg·hr/mL) |
CL/F (L/h) |
t½b (h) |
|---|---|---|---|---|---|---|---|---|
| 10 mg | −3 | 3 | 6·7 ± 1·2 | 0·18 ± 0·05 | 2·2 ± 0·4 | 3·2 ± 1·1 | 3·4 ± 1·2 | 13·8 ± 5·8 |
| 1 | 3 | 11·3 ± 11 | 0·12 ± 0·03 | 1·5 ± 0·5 | – | – | – | |
| 14 | 3 | 5·0 ± 2·6 | 0·19 ± 0·06 | – | – | – | – | |
| 20 mg | −3 | 3 | 7·3 ± 1·2 | 0·29 ± 0·13 | 3·9 ± 1·8 | 6·4 ± 3·1 | 3·7 ± 2·0 | 19·1 ± 3·3 |
| 1 | 3 | 4·0 ± 1·7 | 0·36 ± 0·18 | 4·2 ± 2·1 | – | – | – | |
| 14 | 3 | 4·3 ± 1·5 | 0·48 ± 0·31 | – | – | – | – | |
| 40 mg | −3 | 3 | 7·3 ± 1·2 | 0·37 ± 0·13 | 5·0 ± 1·6 | 8·4 ± 3·4 | 5·3 ± 2·1 | 20·2 ± 4·6 |
| 1 | 3 | 6·0 ± 2·0 | 0·50 ± 0·15 | 6·4 ± 1·2 | – | – | – | |
| 14 | 3 | 6·7 ± 1·2 | 0·65 ± 0·37 | – | – | – | – | |
| 80 mg | −3 | 3 | 8·0 ± 0·0 | 0·85 ± 0·39 | 11·9 ± 5·8 | 17·6 ± 9·3 | 5·3 ± 2·3 | 14·7 ± 1·0 |
| 1 | 2c | 7·0 ± 1·4 | 1·68 ± 0·79 | 21·1 ± 10·7 | – | – | – | |
| 14 | 3 | 7·3 ± 1·2 | 1·80 ± 0·97 | – | – | – | – | |
| 160 mg | −3 | 5d,e | 8·0 ± 0.0 | 1·49 ± 0·50 | 18·8 ± 4·4 | 32·5 ± 7·8 | 5·1 ± 1·2 | 20·2 ± 5·5 |
| 1 | 6e | 9·7 ± 7·1 | 2·05 ± 0·59 | 25·9 ± 5·5 | – | – | – | |
| 14 | 5e | 6·0 ± 1·4 | 2·78 ± 0·46 | – | – | – | – | |
| 225 mg | −3 | 4 | 7·5 ± 1·0 | 2·39 ± 0·60 | 31·7 ± 7·8 | 46·5 ± 12·4 | 5·1± 1·5 | 16·2 ± 2·8 |
| 1 | 4 | 7·5 ± 1·0 | 3·08 ± 0·82 | 43·9 ± 9v5 | – | – | – | |
| 14 | 3 | 7·3 ± 1·2 | 4·64 ± 1·57 | – | – | – | – | |
| 315 mg | −3 | 8c | 11·8 ± 7·6 | 3·56 ± 1·11 | 50·5 ± 15·6 | 91·0 ± 33·5 | 4·1 ± 2·1 | 15·1 ± 3·0 |
| 1 | 9 | 7·6 ± 1·0 | 4·35 ± 1·06 | 58·5 ± 17·5 | – | – | – | |
| 14 | 8 | 5·3 ± 2·8 | 6·44 ± 3·18 | – | – | – | – | |
| 440 mg | −3 | 5 | 10·8 ± 7·4 | 3·51 ± 1·50 | 57·6 ± 21·0 | 128·6 ± 30·4 | 3·6 ± 0·8 | 21·1 ± 2·8 |
| 1 | 5 | 17·2 ± 9·3 | 4·17 ± 2·08 | 72·5 ± 39·3 | – | – | – | |
| 14 | 5 | 4·4 ± 4·1 | 3·19 ± 1·56 | – | – | – | – | |
| All doses | −3 | 34 | 8·9 ± 4·8 | – | – | – | 4·5 ± 1·7 | 17·1 ± 4·3 |
| 1 | 35 | 9·0 ± 6·2 | – | – | – | – | – | |
CL/F = apparent oral clearance, t1/2 = half-life
a
Dosing under fasting (Day –3) and nonfasting (Days 1 through 14) conditions. Pharmacokinetic parameters for Day computed using concentration values adjusted for carryover for the dose on Day -3.
b
Harmonic mean ± pseudo standard deviation.