Table 3.
Oral pharmacokinetics of FLT3 inhibitors
| Compound | Dose, mg/kg | Cmax, μM | Tmax, h | AUC0-24 h, μM×h |
|---|---|---|---|---|
| AC220 | 10 | 3.8 ± 0.4 | 1.5 ± 0.9 | 35 ± 4 |
| CEP-701 | 10 | 0.14 ± 0.06 | 0.92 ± 0.9 | < 0.88† |
| MLN-518 | 10 | 0.081 ± 0.003 | 1.0 ± 0 | 0.28 ± 0.03 |
| PKC-412* | 10 | 0.77 ± 0.04 | 0.67 ± 0.3 | 2.5 ± 0.4 |
| CGP-52421 | From PKC-412* | 2.3 ± 0.3 | 0.67 ± 0.3 | 8.4 ± 1 |
| Sorafenib | 10 | 12 ± 2 | 3.0 ± 3 | 240 ± 50 |
| Sunitinib | 10 | 0.32 ± 0.06 | 1.2 ± 0.8 | 1.1 ± 0.3 |
Values shown are averages from 3 independent time courses (± SD).
*
PKC-412 and CGP-52421 were quantitated independently after dosing PKC-412.
†
The plasma concentration of CEP-701 was below the limit of detection at 24 hours.