Table 1.
DMPK profile of ML381.
| Species | Property | Value1 |
|---|---|---|
| Sprague Dawley Rat | Hepatic Microsomal CLint | 770 mL/min/kg |
| Predicted CLhep | 64 mL/min/kg | |
| fuplasma; fubrain | 0.582; 0.14 | |
| Cbrain:Cplasma (Kp) | 0.583 | |
|
| ||
| Human | Hepatic Microsomal CLint | 93 mL/min/kg |
| Predicted CLhep | 17 mL/min/kg | |
| fuplasma | 0.112 | |
| MDCK-MDR1 ER | 1.6 | |
| P450 1A2 IC50 | > 30 μM | |
| P450 2C9 IC50 | 6.3 μM | |
| P450 2D6 IC50 | > 30 μM | |
| P450 3A4 IC50 | 27 μM | |
1
values represent means of at least two replicates with similar results
2
fuplasma values not accurate due to instability in rat plasma
3
Kp determined at 0.25 hr following a 0.2 mg/kg IV dose (n = 2)