Peak ID

Single dose %ODRMa (% of parent)

Repeat dose %ODRMa (% of parent)

Exposure multipleb rat vs human

Exposure multipleb dog vs human

Exposure multipleb rabbit vs human

Parent

12

1

M = 13

F = 10

M = 17

F = 15

1

SB636406

N-dealkylation

8

(67)

54

(5400)

M = 0.1

F = 0.1

M = 0.1

F = 0.1

0.2

M3

N,N-debutylation

17

(142)

4

(400)

M = 1

F = 1

M = 2

F = 1

1

M18

Oxidation

16

(133)

9

(900)

M = 4

F = 9

M = 0.7

F = 0.4

0.3

M59

N,N-debutylation, hydroxylation and
O-glucuronidation

6

(50)

2

(200)

NA

M = 0.05

F = 0.03

0.1

For exposure estimates rounding of data was carried out at the final stage for presentation purpose only and minor numerical differences may be observed.
ODRM = Observed Drug Related Material
aDetermined by 19F NMR integration.
b0-24 hours proportional pool after repeat dosing in rat, dog, rabbit (at the NOAEL) and human (at 120 mg BID)
NA = Not Applicable. M59 was not detected in rat plasma.
M = Male
F = Female
Table 1: Notable Human Metabolites Identified in Pooled Plasma Extracts and Their Exposure Ratio Estimates in Pooled Plasma of Preclinical Species.