Table 3. In Vitro and In Vivo Characterization of 2b, 2d, and 3.
2b | 2d | 3 | |
---|---|---|---|
CYPa IC50 (μM) | |||
3A4/2D6 | > 40 > 40 | > 40 > 40 | > 40 > 40 |
2C9/2C19 | > 40 > 40 | > 40 > 40 | > 40 > 40 |
hERG patch clamp: % Inh @ 30 μM | 24 | 19 | 36 |
Na+ patch clamp: % Inh @ 30 μM, 4 Hz | 2.5 | 13 | 65 |
protein binding %free: | |||
human/cyno/dog | 50/65/78 | 59/49/51 | |
rat/mouse | 53/51 | 53/47 | |
mouse PK data (IV: 2 mg/kg; PO: 10 mg/kg) | |||
AUC0–24h (μM·h)/F (%) | 2.0/38 | 5.4/93 | |
Cl (mL/min/kg)/T1/2 (h) | 70/2.6 | 63/4.1 |
CYP = cytochrome P450.