TABLE 4.
In vitro ADME profile of BI 224436
| Assay or parameter | Value(s) for BI 224436 |
|---|---|
| Solubility (μg/ml) at pH 2, 4.5, 6.8 (crystalline) | 840, >780, >1,000 |
| Caco-2 cell permeability, A to B and B to A (10−6 cm/s) | 13 and 3.9 |
| P450 IC50 (μM) for 2C9, 3A4BFC, 1A2, 2C19, 2D6 | 20, 23, >30, >30, >30 |
| PK parameter (H, M, R, Mnk, D)a | |
| Phase I LM CL (%QH) | 14, 6.4, 7, 11, 16 |
| Hepatic CL (%QH) | 13, 12, 9, 13, 32 |
| Phase II LM CL (%QH) | <11, <6, <6, <7, 20 |
| Plasma protein binding (%) | 84.3, 97.3, 98.2, 78.0, 75.5 |
a
H, M, R, Mnk, and D correspond to human, mouse, rat, monkey, and dog, respectively.