TABLE 5.
PK profile of BI 224436 after 1-mg/kg i.v. and 2-mg/kg oral doses
| Test species | Protein binding (%) | CL (ml/min/kg) (% QH) | Vss (liter/kg) | t1/2 (h) | Cmax (μM) | AUC (μM · h) | F (%) |
|---|---|---|---|---|---|---|---|
| Mouse | 97.3 | 0.7 (0.8) | 0.20 | 2.6 | 15a | 99a | 100 |
| Rat | 98.2 | 0.5 (0.7) | 0.45 | 8.8 | 13a | 75a | 54 |
| Monkey | 78.0 | 11 (23) | 0.54 | 1.4 | 4.8 | 6.3 | 82 |
| Dog | 75.5 | 2.5 (8) | 0.88 | 5.9 | 12 | 24 | 81 |
a
A mouse and rat oral dose of 0.4 mg/kg was dose normalized to 2 mg/kg to allow for an appropriate comparison to monkey and dog PK studies. The oral formulation contained 1% MP, 0.3% Tween 80, 0.5% MC; the i.v. formulation contained 70% PEG, 30% water.