Table 2. Mean Pharmacokinetic Parameters of TG8-260 (2f) Following Single-Dose Administration by iv, ip, and po Routes of Delivery to Male Mice and Ratsa.
| species | route | dose (mg/kg) | Tmax1 (Tmax2) (h) | Cmax1 (Cmax2) (μg/mL) | AUClast (h*μg/mL) | AUCinf (h*μg/mL) | T1/2 (h) | CL (mL/min/kg) | Vss (L/kg) | %F | B/P ratio |
|---|---|---|---|---|---|---|---|---|---|---|---|
| mouse | iv | 5 | 0.08 | 4.7 | 4.8 | NC | 1.47 | 16.8 | 1.29 | ND | |
| mouse | ip | 20 | 1.0 | 12.5 | 37.8 | 38 | 2.82 | 8.79 | 2.14 | 52 | 0.02 |
| rat | iv | 5 | 0.08 | 4.3 | 5.56 | NC | 1.71 | 14.8 | 1.37 | ND | |
| rat | po | 25 (BID = 50) | 0.5 (8.5) | 5.3 (5.9) | 43 | 43 | 2.14 | 9.65 | 1.79 | 77.3 | 0.02 |
a
Formulation of the dosing vehicle used for iv, ip, and po deliveries: 5% NMP, 5% Solutol-HS15, and 90% normal saline. Dose volume 5 mL/kg (iv), 10 mL/kg (ip and po), n = 3 mice/rats per time point. CL, total plasma clearance; Vss, volume of distribution at steady state; %F, bioavailability; B/P, brain-to-plasma ratio; Tmax, time taken to reach maximum plasma concentration; Cmax, highest plasma concentration; T1/2, half-life; ND, not determined; NC, not calculated; and B.I.D., two doses 8 h apart (see Figure 3).