Table 2. In vitro ADME and pharmacokinetics of INCB054828.
| In Vitro ADME | |||
| Caco-2 (Papp 10−6 cm/sec; A–B at 50 μM) | 11 | ||
| Intrinsic clearance (L/h/kg)a | 0.8 | ||
| PPB (% free; rat, monkey, human at 1 μM) | 3.0, 8.2, 11.3 | ||
| CYP3A4 inhibition (IC50, μM) | >25 | ||
| Pharmacokineticsb | |||
| Rat | Dog | Monkey | |
| CL (L/h/kg)c | 1.03 | 0.183 | 0.198 |
| Hepatic ER (%)c | 31 | 10 | 8 |
| Vss (L/kg)c | 1.85 | 3.49 | 0.584 |
| t½(h)c | 4.0 | 15.7 | 10.3 |
| Cmax (μM)d | 2.26 | 1.77 | 0.766 |
| AUC (μM*h)d | 7.67 | 22.1 | 6.19 |
| %Fd | >100 | 98 | 29 |
aStudy conducted with human liver microsomes.
bDetermined from dosing the male animals.
cIntravenous dose levels– 1 mg/kg.
dOral dose levels– 2 mg/kg.
AUC, area under the concentration-time curve; CL, clearance; Cmax, maximum plasma drug concentration; ER, extraction ratio; F, bioavailability; PPB, plasma protein binding; Papp, apparent permeability; t½, half-life; Vss, steady-state volume or distribution.