Pharmacokinetics of GDC-0834 in CD-1 mice, Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys
Data are means ± S.D. Oral data are from GDC-0834 dosed orally as follows: for mouse, as solution (free base) in 20% Cremophor EL/10% ethyl alcohol; for rat, as a crystalline suspension (free base) in MCT; for dog, as a crystalline suspension (free base) in MCT after pretreatment with pentagastrin; and for monkey, as solution (free base) in 60% PEG 400.
| Parameters | Mouse | Rat | Dog | Monkey |
|---|---|---|---|---|
| Intravenous administration | ||||
| No. of animals | 24 (3/time point) | 3 | 3 | 3 |
| Sex | Female | Male | Male | Male |
| Dose, mg/kg | 1 | 1 | 1 | 1 |
| CL, ml · min−1 · kg−1 | 43.0 | 4.66 ± 4.81 | 13.6 ± 2.34 | 32.7 ± 3.06 |
| t1/2, h | 0.158 | 1.09 ± 0.503 | 0.789 ± 0.0705 | 0.615 ± 0.0548 |
| MRT, h | 0.156 | 1.29 ± 0.579 | 0.933 ± 0.0907 | 0.745 ± 0.131 |
| Vss, l/kg | 0.402 | 0.253 ± 0.129 | 0.755 ± 0.0655 | 1.46 ± 0.312 |
| Renal clearance, ml · min−1 · kg−1 | N.A.a | N.A.a | N.A.b | 0.00127c |
| Oral administrationd | ||||
| No. of animals | 24 (3/time point) | 3 | 3 | 3 |
| Sex | Female | Male | Male | Male |
| Dose, mg/kg | 5 | 5 | 5 | 5 |
| Cmax, ng/ml | 351 | 1330 ± 494 | 651 ± 128 | 198 ± 46.0 |
| tmax, h | 0.500 | 1.33 ± 0.577 | 0.750 ± 0.433 | 1.33 ± 0.577 |
| AUC0–∞, h · ng/ml | 348 | 5310 ± 1340 | 1990 ± 660 | 393 ± 89.1 |
| F, % | 17.9 | 16.1 ± 4.06 | 31.9 ± 10.6 | 15.5 ± 4.23 |
AUC0−∞, area under the concentration-time curve, extrapolated to infinity; MCT, 0.5% weight/volume ratio methylcellulose with 0.2% volume to volume ratio polysorbate 80 in water; MRT, mean residence time; N.A., not available; PEG, polyethylene glycol; tmax, time to maximum concentration.
a No urine was collected.
b Data were not reportable.
c Renal clearance was assessed for the intravenous group only.
d Oral data were from GDC-0834 dosed orally.