Pharmacokinetics (mean ± SD) of GDC-0917 in the mouse, rat, dog, and monkey
| Parameters | Mouse | Rat | Dog | Monkey |
|---|---|---|---|---|
| Intravenous administration | ||||
| No. of animals | 27 (3/time point) | 3 | 3 | 3 |
| Sex | Female | Male | Male | Male |
| Dose (mg/kg) | 1 | 1a | 1 | 1 |
| CL (ml/min/kg) | 12.0 | 27.0 ± 1.91 | 15.3 ± 0.643 | 67.6 ± 6.17 |
| t1/2 (h) | 1.47 | 0.900 ± 0.0862 | 6.12 ± 4.22 | 0.825 ± 0.0634 |
| MRT (h) | 1.76 | 1.12 ± 0.0945 | 4.44 ± 2.38 | 1.05 ± 0.112 |
| Vss (l/kg) | 1.27 | 1.81 ± 0.0529 | 4.09 ± 2.27 | 4.25 ± 0.352 |
| Oral administration | ||||
| No. of animals | 27 (3/time point) | 3 | 3 | 3 |
| Sex | Female | Male | Male | Male |
| Dose (mg/kg) | 3 | 5a | 1 | 2 |
| Cmax (ng/ml) | 884 | 545 ± 261 | 254 ± 129 | 33.6 ± 10.3 |
| tmax (h) | 0.500 | 2.00 ± 1.73 | 1.00 ± 0.00 | 1.33 ± 0.577 |
| AUCinf (ng • h/ml) | 3870 | 2390 ± 976 | 1060 ± 606 | 83.2 ± 12.2 |
| F (%) | 93.5 | 77.0 ± 31.4 | 97.0 ± 55.6 | 16.8 ± 2.45 |
| Renal clearance (ml/min/kg) | NA | NA | 0.0897 ± 0.0980b | 1.44 ± 1.72c |
AUCinf, area under the concentration–time curve from zero to infinity; CL, plasma clearance; Cmax, highest observed plasma concentration; F, bioavailability; MRT, mean residence time; NA, not available; t1/2, half-life; tmax, time at which Cmax occurred; Vss, volume of distribution at steady state.
↵a Free-base equivalent (trifluoroacetate salt of GDC-0917 was administered).
↵b Renal clearance was assessed for PO group only.
↵c Renal clearance was assessed for i.v. group only.