Table 9. In Vivo PK Characterization of TNG908.
| species | clearance (mL/min/kg) | Vss (L/kg) | T1/2 (h) | F (%) | Kp,uu,CSFd |
|---|---|---|---|---|---|
| rata | 38.2 | 1.5 | 2 | >100 | |
| dogb | 8.6 | 1.2 | 4 | 41 | |
| cynomolgus monkeyc | 16.2 | 1.0 | 1 | 21 | 0.9 |
IV/PO dosing in Sprague–Dawley rat (vehicle, IV, 1 mg/mL solution of 1% v/v DMSO/99% of 20% w/v HP-β-CD in saline; PO, 3 mg/mL solution of 1% v/v DMSO/99% of 20% w/v HP-β-CD in water, n = 3 per arm).
IV/PO dosing in beagle dog (vehicle, IV, 1 mg/mL solution of 1% v/v DMSO/99% of 20% w/v HP-β-CD in saline; PO, 3 mg/mL solution of 1% v/v DMSO/99% of 20% w/v HP-β-CD in water, n = 3 per arm).
IV/PO dosing in cynomolgus monkey (vehicle, IV, 1 mg/mL solution of 1% v/v DMSO/99% of 20% w/v HP-β-CD in saline; PO, 3 mg/mL solution of 1% v/v DMSO/99% of 20% w/v HP-β-CD in water, n = 3 per arm).
PO dosing in cynomolgus monkeys (vehicle, PO, 0.5% methylcellulose in water, n = 3), Kp,uu,CSF determined by measuring CSF concentration and taking the ratio to free unbound plasma concentrations.