Table 1.

Pharmacokinetics of ABT-888 in mice, Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys

i.v. Dose
Strain
Dose (mg/kg)
t1/2 (h)
Vc (L/kg)
Vss (L/kg)
Vβ (L/kg)
AUC (μg·h/mL)
CLp (L/h·kg)
Mouse CD-1101.62.12.59.42.434.1
Rat51.21.63.13.62.462.0
Dog2.52.71.42.02.24.420.6
Monkey2.51.92.02.83.12.361.1
Oral dose
Strain
Dose* (mg/kg)
Cmax (μg/mL)
Tmax (h)
t1/2 (h)
AUC0-12h (μg·h/mL)
F (%)
Mouse CD-1101.60.31.32.2492
Rat50.50.81.61.5262
Dog2.52.70.80.53.2273
Monkey2.52.50.32.31.3356
Nude12.50.80.71.01.30
Scid12.50.70.70.80.80
C57BL/612.51.20.31.41.50
OMP

Dose (mg/kg)Nude
Scid
C57BL/6


Css (μg/mL)
AUC0-24h (μg·h/mL)
Css (μg/mL)
AUC0-24h (μg·h/mL)
Css (μg/mL)
AUC0-24h (μg·h/mL)
500.2616.260.2325.560.1052.52
250.1814.340.1293.100.0461.10
12.50.0731.750.0852.04
50.0220.53
3.1250.0230.550.0170.41
  • * In tumor models, the oral dose is administered b.i.d, so the total daily dose in milligrams per kilogram is doubled. Likewise, the AUC0-12h is multiplied by two to yield the total daily AUC.