GSK356278 (0.003-30 mg/kg; p.o.) shows anti-inflammatory activity in rodents at exposures that does not induce pica feeding.
GSK356278 (0.1-0.1 mg/kg; p.o.) demonstrates efficacy in a nonhuman primate model of anxiety at exposures that do not induce emesis.
GSK356278 (4 doses at 0.03, 0.1, 0.3, and 1.0 mg/kg for 6 weeks; p.o.) enhances performance in a nonhuman primate object retrieval test.
GSK356278 exhibits oral bioavailability (rat 91%, monkey 23%) and Cmax (rat 205, monkey 41 nM) following oral administration (rat 1, monkey 0.2 mg/kg).
GSK356278 exhibits terminal elimination half-lives (rat 2.2, monkey 1.5 h) due to moderate blood clearance (rat 40, monkey 16 mL/min/kg) combined with volumes of distribution (rat 6.3, monkey 2.1 L/kg) following intravenous administration (rat 1, monkey 0.2 mg/kg).
Animal Model: |
Male Lewis rats (320-400 g) are treated with lipopolysaccharide (LPS) |
Dosage: |
0.003-3 mg/kg |
Administration: |
P.o. administration 30 minutes prior to the LPS challenge |
Result: |
Reduced the level of neutrophilia in a dose-dependent manner, with an ED50 of 0.09 mg/kg. |
Animal Model: |
Male CD rats |
Dosage: |
1 mg/kg (Pharmacokinetic Analysis) |
Administration: |
I.v. and p.o. administration |
Result: |
Oral bioavailability (91%), Cmax (205 nM), T1/2 (2.2 h). |