Table 2.
PK/PD model values from mouse and rat studies.
| Parameter | Units | Mouse | CV (%) | Rat | CV (%) |
|---|---|---|---|---|---|
| PK parameters | |||||
| Kel | h−1 | 0.28 | 44.1 | 0.10 | 48.4 |
| V/F | L/kg | 1.94 | 48.3 | 1.94 | 43.8 |
| Ka1 (10 mg/kg) | h−1 | 0.19 | 56.0 | ||
| Ka1 (30 mg/kg) | h−1 | 0.11 | 29.8 | ||
| Ka2 (100 mg/kg) | h−1 | 0.046 | 30.0 | ||
|
| |||||
| PD parameters | |||||
| K OUT | h−1 | 0.72 | 24.9 | 0.48 | 51.4 |
| IC50
|
nM | 3979 | 9.16 | 1892 | 26.4 |
| R0 | % | 100 | Fixed | 100 | Fixed |
|
I
max
|
1 | Fixed | 1 | Fixed | |
|
K
in
|
%/h | 72 | Calculated | 48 | Calculated |
Kel-first order rate constant for drug elimination; V-volume of distribution; Ka rate constant for drug absorption; K OUT-first order rate constant for degradation of Aβ1-42 or Aβ1-40; IC50-plasma concentration required for 50% inhibition of Aβ1-42 or Aβ1-40 production; R is the response in Aβ1-42 or Aβ1-40 levels, assumed 100% at time zero, R0; I max-range of the response of Aβ1-42 or Aβ1-40 levels; K in-zero order constant for Aβ1-42 or Aβ1-40 production.