Table 2 Summary of SPI-1865 PK/PD studies in wild-type and transgenic mouse and wild-type rat

Wild-type rat single dose

10

Brain

3.3 ± 0.1

2.8 ± 0.3

26 ± 5

1 ± 5

21 ± 6*

24

30

Brain

8.5 ± 0.3

11 ± 1

36 ± 3*

14 ± 4

37 ± 5*

24

100

Brain

14 ± 1

33 ± 2

47 ± 5*

22 ± 5*

50 ± 5*

24

Wild-type rat multiple doses

10

Brain

8.0 ± 0.4

4.4 ± 0.2

27 ± 3*

1 ± 2

24 ± 2*

24

30

Brain

13 ± 1

16 ± 1

49 ± 2*

8 ± 3

44 ± 2*

24

60

Brain

19 ± 1

45 ± 4

61 ± 2*

26 ± 2*

66 ± 1*

24

Tg2576 mouse multiple doses

10

Brain

1.1 ± 0.2

0.5 ± 0.1

-16 ± 12

-14 ± 11

-9 ± 10

24

30

Brain

2.5 ± 0.1

1.3 ± 0.1

6 ± 9

6 ± 9

7 ± 9

24

60

Brain

5.4 ± 0.5

3.9 ± 0.4

14 ± 10

2 ± 10

19 ± 8

24

90

Brain

6.4 ± 0.5

6.9 ± 0.6

27 ± 8

8 ± 9

30 ± 6

24

10

Plasma

1.1 ± 0.2

0.5 ± 0.1

25 ± 5

6 ± 7

25 ± 5*

24

30

Plasma

2.5 ± 0.1

1.3 ± 0.1

26 ± 5

17 ± 5

58 ± 3*

24

60

Plasma

5.4 ± 0.5

3.9 ± 0.4

50 ± 5*

15 ± 7

71 ± 2*

24

90

Plasma

6.4 ± 0.5

6.9 ± 0.6

46 ± 6*

9 ± 6

76 ± 2*

24

10

CSF

1.1 ± 0.2

0.5 ± 0.1

-2 ± 9

-3 ± 9

1 ± 11

24

30

CSF

2.5 ± 0.1

1.3 ± 0.1

4 ± 10

0 ± 11

6 ± 11

24

60

CSF

5.4 ± 0.5

3.9 ± 0.4

5 ± 9

-7 ± 12

22 ± 15

24

90

CSF

6.4 ± 0.5

6.9 ± 0.6

9 ± 11

10 ± 13

33 ± 14

24

Wild-type mouse multiple twice-daily doses

15

Brain

3.4 ± 0.2

3.6 ± 0.1

13 ± 4

3 ± 2

22 ± 4*

6

30

Brain

4.4 ± 0.3

8.7 ± 1.0

30 ± 3*

11 ± 2*

39 ± 3*

6

50

Brain

7.6 ± 0.3

22 ± 1

28 ± 2*

9 ± 2

47 ± 2*

6