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. 2024 Apr 10;67(8):6064–6080. doi: 10.1021/acs.jmedchem.4c00133

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
a

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).

b

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).

c

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).

d

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.