Table 3. Cross-Species Pharmacokinetics of 13 (GNE-495) Following Dosing via IV and PO Routesa.
| IV bolus
(1 mg/kg); solutionb |
PO
(5 mg/kg); suspensionc |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| species | %PPB | CL (mL/min kg–1) | T1/2 (h) | Cmax (μM) | V (L/kg) | AUCinf (h·μM) | Cmax (μM) | Tmax (h) | F% | Cu,brain (μM) |
| mouse | 94.4 | 19 | 1.5 | 2.7 | 1.6 | 5.3 | 1.4 | 1.0 | 47 | 0.008 |
| rat | 97.8 | 7.5 | 3.4 | 4.0 | 1.2 | 12.0 | 1.5 | 4.0 | 40 | N.D. |
| dog | N.D. | 8.9 | 1.8 | 3.9 | 1.1 | 21.0 | 1.2 | 1.7 | 37 | N.D. |
a
Mean values are shown. Further details provided in the Supporting Information.
b
Vehicle: 10% EtOH, 30% PEG400, 60% 50 mM citrate, pH 3.0.
c
Vehicle: 0.5% (w/v) methylcellulose/0.2% (w/v) Tween 80 in sterile water (MCT).