Table 2.
Pharmacokinetic Parameters of Navitoclax After Oral Administration (14/21-day dosing schedule)
| Study Day by Dose (mg) | No. | Tmax (hours) |
Cmax (μg/mL) |
AUC0-24 (μg × hr/mL) |
AUC0-inf (μg × hr/mL) |
CL/F (L/h) |
t1/2* (hours) |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | ||
| 10 | |||||||||||||
| −3 | 4 | 6.0 | 1.6 | 0.13 | 0.04 | 1.4 | 0.4 | 2.0 | 0.6† | 5.3 | 1.4† | 15.3 | 2.2† |
| 14 | 4 | 6.0 | 0.0 | 0.12 | 0.07 | — | — | — | — | — | — | — | — |
| 20 | |||||||||||||
| −3 | 4 | 6.3 | 2.4 | 0.38 | 0.05 | 4.9 | 0.9 | 7.1 | 1.9 | 3.0 | 0.8 | 13.5 | 6.6 |
| 14 | 4 | 7.0 | 1.2 | 0.46 | 0.14 | — | — | — | — | — | — | — | — |
| 30 | |||||||||||||
| −3 | 6 | 6.0 | 1.3 | 0.67 | 0.29 | 7.3 | 3.4 | 10.1 | 4.6 | 5.0 | 5.7 | 14.1 | 10.4 |
| 14 | 5 | 4.4 | 2.1 | 0.81 | 0.21 | — | — | — | — | — | — | — | — |
| 130 | |||||||||||||
| −3 | 4 | 11.0 | 8.7 | 1.84 | 1.22 | 25.4 | 12.8 | 42.0 | 12.4 | 3.3 | 0.8 | 16.9 | 1.2 |
| 14 | 4 | 6.0 | 1.6 | 2.81 | 1.75 | — | — | — | — | — | — | — | — |
| 225 | |||||||||||||
| −3 | 3 | 5.7 | 2.5 | 2.97 | 1.24 | 39.5 | 18.8 | 53.0 | 24.6 | 5.3 | 3.3 | 12.8 | 0.8 |
| 14 | 4 | 7.5 | 1.0 | 5.10 | 0.85 | — | — | — | — | — | — | — | — |
| 325 | |||||||||||||
| −3 | 6 | 10.0 | 6.9 | 2.55 | 1.46 | 40.9 | 25.8 | 80.5 | 44.3‡ | 5.9 | 4.7† | 15.8 | 3.1† |
| 14 | 8 | 5.8 | 2.3 | 4.31 | 2.14 | — | — | — | — | — | — | — | — |
| 425 | |||||||||||||
| −3 | 5 | 5.0 | 2.0 | 3.43 | 1.75 | 53.7 | 30.8 | 99.2 | 69.5 | 7.5 | 6.4 | 15.0 | 3.4 |
| 14 | 3 | 3.7 | 4.0 | 2.87 | 0.78 | — | — | — | — | — | — | — | — |
| 475 | |||||||||||||
| −3 | 3 | 12.0 | 10.4 | 3.76 | 1.71 | 66.8 | 35.6 | 81.0 | 29.7§ | 6.3 | 2.3§ | 15.7 | 0.2§ |
| 14 | 1 | 6.0 | 5.59 | — | — | — | — | — | — | — | — | ||
NOTE. All doses were taken under nonfasting condition.
Abbreviations: Tmax, time to maximum observed plasma concentration; Cmax, maximum plasma concentration; AUC, area under the curve; inf, infinity; CL/F, apparent oral clearance; t1/2, terminal half-life; SD, standard deviation.
*
Harmonic mean ± pseudo SD.
†
N = 3.
‡
N = 5.
§
N = 2.