PK/PD modeling-derived PD parameters in 129/SVE mouse
Parameters are presented as mean estimate (S.E. of estimate); fixed means the parameter was assigned a pharmacologically reasonable value without being estimated by modeling.
| Parameter | Elan-X | GSI-953 | LY450139 | BMS-708163 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CSF Aβ40 | Brain Aβ40 | Brain Aβ42 | CSF Aβ40 | Brain Aβ40 | Brain Aβ42 | CSF Aβ40 | Brain Aβ40 | Brain Aβ42 | CSF Aβ40 | Brain Aβ40 | Brain Aβ42 | |
| Imax | 0.99 (0.01) | 0.85 (0.02) | 0.80 (0.06) | 0.99 (0.17) | 0.81 (0.01) | 0.53 (0.07) | 1 (fixed) | 1 (fixed) | 1 (fixed) | 1 (fixed) | 1 (fixed) | 1 (fixed) |
| γ | 1 (fixed) | 1 (fixed) | 1 (fixed) | 1.02 (0.40) | 0.94 (0.05) | 0.67 (0.14) | 1.40 (0.20) | 0.55 (0.04) | 0.86 (0.13) | 1 (fixed) | 1 (fixed) | 1 (fixed) |
| kout, 1/h | 1.52 (0.16) | 0.79 (0.12) | 0.32 (0.04) | 1.17 (0.26) | 1.07 (0.04) | 0.78 (0.10) | 1.58 (0.26) | 1.08 (0.08) | 0.50 (0.06) | 1.40 (0.19) | 0.61 (0.06) | 0.34 (0.03) |
| IC50, free brain, nM | 19.0 (3.2) | 4.6 (1.2) | 8.4 (2.3) | 213.4 (98.8) | 34.0 (1.9) | 125.7 (59.6) | 192.3 (25.1) | 51.1 (4.9) | 151.2 (19.7) | 21.0 (2.2) | 11.9 (1.1) | 18.3 (1.6) |