Pharmacokinetics of navitoclax and ABT-199 after i.v. (1 mg/kg) and oral (100 mg/dog; ∼10 mg/kg) administration to intact (noncannulated) and thoracic lymph–cannulated fed dogs
Data are presented as mean ± S.D. (n = 3; for each compound the same animals were dosed after a washout period).
| Navitoclax | ABT-199 | |||||
|---|---|---|---|---|---|---|
| i.v. | p.o. | i.v. | p.o. | |||
| Intact | Intact | Thoracic Lymph–Cannulated | Intact | Intact | Thoracic Lymph–Cannulated | |
| AUC0–tlast (μM⋅h) | 26.9 ± 0.2 | 158 ± 24 | 61.2 ± 2.6 | 24.6 ± 4.1 | 92.2 ± 10.2 | 48.6 ± 2.5 |
| AUC0–∞ (μM⋅h) | 26.9 ± 0.2 | 164 ± 24 | 67.3 ± 3.8 | 25.1 ± 4.1 | 94.3 ± 11.0 | 53.5 ± 5.1 |
| CL (ml/min per kg) | 0.673 ± 0.004 | NA | NA | 0.774 ± 0.134 | NA | NA |
| Vss (l/kg) | 0.481 ± 0.031 | NA | NA | 0.729 ± 0.143 | NA | NA |
| T1/2 (hr) | 22.2 ± 1.0 | 17.4 ± 1.9 | 22.9 ± 8.1 | 12.9 ± 0.9 | 12.9 ± 0.9 | 21.4 ± 6.7 |
| Cmax (μM) | NA | 22.5 ± 3.2 | 5.18 ± 1.58 | NA | 5.19 ± 0.37 | 3.16 ± 0.27 |
| Tmax (hr) | NA | 2.0 ± 0.0 | 4.0 ± 2.0 | NA | 4.0 ± 2.0 | 4.67 ± 1.15 |
| F (%) | NA | 56.5 ± 3.8 | 21.7 ± 2.4 | NA | 38.8 ± 7.2 | 20.2 ± 2.1 |
NA, not applicable. Vss, volume of distribution at steady-state