TABLE 5

Pharmacokinetic parameters (mean ± S.D.) of GDC-0980 in mouse, rat, dog, and monkey after intravenous and oral administrations

ParametersNCr Nude MiceSprague-Dawley RatsBeagle DogsCynomolgus Monkeys
No. of animals27* (3/time point)3*33
SexFemaleMaleMaleMale
Dose, mg/kg1111
CL, ml · min−1 · kg−16.3015.4 ± 2.856.38 ± 0.65719.0 ± 1.31
t1/2, h2.053.52 ± 2.396.41 ± 0.8850.558 ± 0.101
Mean residence time, h3.844.38 ± 2.507.57 ± 0.7800.654 ± 0.106
Vss, l/kg1.453.78 ± 1.432.90 ± 0.3970.739 ± 0.0678
Renal clearance, ml · min−1 · kg−1N.D.N.D.N.D.0.405 ± 0.268
Oral administration
No. of animals27§ (3/time point)33§3§
SexFemaleMaleMaleMale
Dose, mg/kg5522
AUCinf, μM·h26.911.8 ± 3.3113.2 ± 0.5450.813 ± 0.302
Cmax, μM4.651.31 ± 0.5332.71 ± 0.5240.438 ± 0.184
tmax, h0.251.17 ± 0.7640.333 ± 0.1441.67 ± 0.577
F, %101106 ± 29.7125 ± 5.1622.9 ± 8.56
  • N.D., not determined.

  • * Doses prepared in 5% dimethyl sulfoxide and 5% cremophor in water.

  • Doses prepared in 30% hydroxypropyl-β-cyclodextrin.

  • Doses prepared in 80% polyethylene glycol 400 in water.

  • § Doses prepared in 0.5% methylcellulose with 0.2% Tween 80.