Table 4. In Vivo Pharmacokinetics of a Set of C2-Fluoro DBFs.
| compound | 31 | 35 | 36 | ||
|---|---|---|---|---|---|
| AMP (permeability, nM/s) | 73 | 45 | 165 | ||
| CLND solubility (μg/mL) | 114 | 174 | 173 | ||
| species | rata | rata | ratb | dogc | |
| IV PK | CL (mL/min/kg) (% LBF) | 98 (120%) | 73 (81%) | 73 (89%) | 3 (5%) |
| Clrenal (mL/min/kg) | 4 | 10 | 4 | 0.3 | |
| Vss (L/kg) | 1.7 | 2.1 | 2.1 | 1.3 | |
| T1/2 (h) | 0.5 | 0.6 | 0.6 | 4.8 | |
| oral PK | Fpo (%) | 15 | 3 | 48 | 87d |
a
n = 1, 1 h IV infusion at 1 mg/kg, n = 3 PO gavage at 3 mg/kg.
b
n = 3, 1 h IV infusion at 1 mg/kg, n = 3 PO gavage at 3 mg/kg.
c
n = 3, 1 h IV infusion at 1 mg/kg, n = 2 PO gavage at 2 mg/kg.
d
Wet Beadmilled Spray Dried material (EXP109376) formulated in 1.5% HPMC PHARMACOAT 603:0.15% (w/v) sodium lauryl sulfate (aq) (1.5: v/v).