Table 7. In Vitro ADME and In Vivo Pharmacokinetic Properties of Select Compounds.
| In Vitro
ADME |
In
Vivo PKd |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| compd | species | cLog D | LM Clint (μL/min)a | Hep Clint (μL/min)b | PPB (% free)c | Dose (iv/po) (mg/kg) | F (%) | AUC (po) (μM·h) | Clp (mL/min/kg) | t1/2 (h) |
| 23 | rat | 1.9 | <12 | 21 | 4.8 | 1/3 | 70 | 1.91 | 50 | 3.6 |
| 30 | rat | 1.7 | 13 | 13 | 11.2 | 1/3 | 21 | 0.51 | 56 | 1.8 |
| 36 | rat | 0.7 | <12 | 34 | 16.1 | 1/3 | 30 | 0.98 | 67 | 2.1 |
| 27 | rat | 2.1 | 17 | 32 | 2.2 | 1/3 | 64 | 2.43 | 33 | 5.0 |
| 27 | mouse | 2.1 | 34 | 68 | 3.0 | 1/3 | 64 | 1.63 | 52 | 5.5 |
a
Intrinsic clearance rate in liver microsomes (μL/min/mg protein).
b
Intrinsic clearance in hepatocytes (μL/min/106 cells).
c
Plasma protein binding, expressed as percent free (unbound) compound.
d
See Supporting Information for PK experiment details.