Table 5.
Sample |
Logan analysisa |
PK modelinga(2T4K) |
Nonlinear mixed effects modeling |
||||
---|---|---|---|---|---|---|---|
WB* | Cer | WB* | Cer | WB* | WB | Cer | |
Control rats |
|
|
|
|
|
|
|
Baseline |
1.6 (16) |
2.0 (19) |
1.8 (16) |
2.2 (18) |
1.5 (18) |
1.6 (18) |
0.81 (20) |
Post-inhibition |
7.6 (13) |
6.1 (9) |
7.8 (14) |
6.1 (9) |
7.0 (19) |
9.6 (18) |
2.4 (21) |
Increase after 3 mg/kg tariquidarb |
4.8-fold |
3.1-fold |
4.4-fold |
2.8-fold |
4.6-fold |
6.2-fold |
4.4-fold |
48-h post SE rats |
|
|
|
|
|
|
|
Baseline |
1.4 (8) |
1.3 (7) |
1.5 (12) |
1.5 (6) |
1.5 |
1.6 |
0.81 |
Post-inhibition |
7.4 (11) |
3.5 (13) |
7.6 (12) |
3.6 (14) |
7.0 |
9.6 |
2.4 |
Increase after 3 mg/kg tariquidarb |
5.5-fold |
2.6-fold |
5.1-fold |
2.4-fold |
4.6-fold |
6.2-fold |
4.4-fold |
Human |
|
|
|
|
|
|
|
Baseline scan |
0.64 (1) |
|
0.65 (6) |
- |
0.54 (−) |
0.51 (−) |
- |
Post-inhibition |
0.79 (1) |
|
0.80 (2) |
- |
0.49 (−) |
0.79 (−) |
- |
Increase after 2 mg/kg tariquidarb | 1.2-fold | 1.2-fold | - | No difference | 1.5-fold | - |
VT values were expressed as average and relative standard errors (%) for the WB region and Cer at baseline and post-inhibition scan. aLogan and 2T4K results were obtained from Bankstahl et al. [9] for rats and from Wagner et al. [30] for humans. bIncrease after tariquidar administration for NLME modeling is based on the estimated covariate effect Efftariquidar(1/Efftariquidar).