Table 4. In Vitro DMPK of Selected Compounds.
| Intrinsic
Clearance (mL/min/kg)a,b |
|
|||||
|---|---|---|---|---|---|---|
| Human |
Mouse |
Plasma
Protein Binding (%fu)a,c |
||||
| Cmpd | CLINT | CLHEP | CLINT | CLHEP | Human | Mouse |
| 1 | 29.6 | 12.3 | 149.5 | 56.2 | 8.5 | 5.6 |
| 11a | 178.6 | 18.8 | 157.4 | 57.3 | 2.6 | 0.6 |
| 11f | 194.3 | 19.0 | 1213.7 | 83.8 | 3.9 | 3.0 |
| 11h | 97.1 | 17.3 | 100.0 | 47.4 | 3.8 | 2.7 |
| 11i | 295.6 | 19.6 | 1142.5 | 83.5 | 2.3 | 2.2 |
| 14a | 172.5 | 18.7 | 551.4 | 77.4 | 1.1 | 0.6 |
| 14i | 33.3 | 12.5 | 104 | 48.2 | 11.3 | 5.1 |
| 14j | 31.5 | 12.6 | <49.5 | <31.9 | 23.5 | 9.6 |
| 14x | <23.1 | <11 | 133.7 | 53.8 | 4.9 | 6.6 |
| 14z | <23.1 | <11 | <49.5 | <31.9 | 47.4 | 39.3 |
| 14bb | <23.1 | <11 | <49.5 | <31.9 | 30.2 | 13.3 |
| Stability in Human Hepatocyte S9 Fractions | |||
|---|---|---|---|
| t1/2 (min) | CLHEP (mL/min/kg) | ER | |
| 11h | 49.4 | 12.6 | 0.63 |
a
In vitro DMPK studies performed at Q2 Solutions, Indianapolis, IN.
b
Intrinsic and predicted hepatic clearance based on experiments in liver microsomes.
c
%fu = % fraction unbound.