Species
(Duration)

Dose
(mg/kg/day)

Sex

Cmax (µg/mL)

AUC0-24 (µg.h/mL)

Day 1a

End of Study

Day 1a

End of Study

Rat
(6 weeks)

15

30

F

5.37

4.06

103

45.9

M

10.5

4.45

121

28.7

50

150

F

22.1

15.9

424

221

M

36.3

15.3

465

120

Dog
(7 Days)

20

M

5.32

4.72

42.2

39.2

F

14.8

6.12

71.8

31.7

50

M

21.1

7.80

151

46.8

F

25.7

7.22

236

41.1

100

M

15.2

11.0

184

62.5

F

15.0

13.4

95.5

36.4

Rabbit
(EDF)

20

F

8.03

-

73.1

-

60

F

24.6

-

246

-

Human
(repeat dose)

240 mgb (120mg BID)

M

0.149c

6.37c

1.75c

68.5c


Note: End of study was Day 43 for rats, Day 7 for dogs and Day 14 for humans
The no adverse effect levels (NOAELs) are in bold type
EDF = Embryofetal development
aDay 5 of dosing (Day 11 postcoitum) for rabbit
bGSK1018921 administered in the repeat dose study
c Estimates of metabolite exposure in terms of theoretical Cmax or AUC0-24 were calculated from clinical Cmax and AUC0-24 data of parent considering % of observed drug
related material
Table 4: Mean Systemic Exposure to SB636406 Following Repeat Oral Administration of SB636406 to Rats, Dogs and Pregnant Rabbits.