Table 6. In Vivo PK and PD Study of 18ea.
| rat PK (10 mpk) | in vivo 11β-HSD1 inhibition (po) in mice (ex vivo) | monkey PK (10 mpk) | in vivo 11β-HSD1 inhibition (po) in monkey (ex vivo) |
|---|---|---|---|
| po Cmax = 3.1 μg/mL | (1 mpk) fat (76.6 ± 2.8%) | po Cmax = 6.4 ug/mL | 10 mpk |
| t1/2 = 3.8 h | (5 mpk) fat (90.4 ± 0.6%)* | t1/2 = 3.4 h | shoulder fat 87% |
| AUC = 15.7 μg h/mL | (10 mpk) fat (90.7 ± 2.6%)* | AUC = 35.6 μg h/mL | Inguinal fat 83% |
| Cl (L/h/kg) = 0.7 | (20 mpk) fat (95.9 ± 0.8%)*** | abdominal cavity fat 81% | |
| F = 68.8% |
a
Results of in vivo 11β-HSD1 inhibition in rats (?) are expressed as means ± SEMs for n = 4 mice per group. In in vivo 11β-HSD1 inhibition in monkeys, results are expressed as means for n = 2 monkey per group *P < 0.05, and ***P < 0.001 vs vehicle group.