Table 9. Summary of Physiochemical and Pharmacokinetic Properties of INE963 (1).
| assay | INE963 (1) data |
|---|---|
| physical form by XRPD | free base; highly crystalline |
| pKa | 4.0, 8.7 |
| log D7.4 | 3.1 |
| solubility in water (mg/mL) | 0.0002 |
| solubility in FaSSIF pH 6.5 (mg/mL) | 1.3 |
| solubility SGF pH 2.0 (mg/mL) | >2 |
| permeability (MDCK-LE; Papp AB × 106 cm/s) | 9.9 |
| CYP inhibition (2C9, 2C19, 2B6, 2C8, all others >20 μM) | 4.5, 5.4, 6.0, 8.5 |
| efflux ratio (MDR1-MDCK; BA/AB) | 11.8 |
| biopharmaceutical class (BCS class) | III (up to 1000 mg dose) |
| mouse, rat, dog, human PPB (% bound) | >99, >99, >99, >99 |
| mouse, rat, dog, human microsome CLint (μL/min/mg) | <25, 29, <25, 25.4 |
| rat, dog, human hepatocyte CLint (μL/min/106 cells) | 7.1, <4, <4 |
| mouse, rat, dog in vivo CL (mL/min/kg)a | 4.0, 5.9, 5.4 |
| mouse, rat, dog in vivoVss (L/kg)a | 7.0, 8.3, 6.3 |
| mouse, rat, dog in vivo half-life T1/2 (h)a | 22.5, 20.4, 15.1 |
| mouse, rat, dog in vivo oral bioavailability (%F)a | 47, 39, 74 |
a
In vivo PK data from a crystalline formate-salt batch of INE963 (1), using blood concentration.