Peak ID

Single dose %ODRMa (% of parent)

Repeat dose %ODRMa (% of parent)

Parent

12

1

M19

Oxidation

ND

<3

(<300)

M24

N,N-debutylation and hydroxyation

<1
(<8)

ND

M27

N,N-debutylation,
O-demethylation,
O-glucuronidation

ND

<1

(<100)

M28

N-dealkylation,
O-demethylation,
O-sulfation

ND

<1

(<100)

M65

Dehydrogenation and hydroxylation

ND

<3

(<300)

M75

N,N-debutylation, oxidation to acid,
di-hydroxylation and
O-glucuronidation

ND

2

(200)

M76

O-demethylated M59

ND

<1

(<100)

M77

N,N-debutylation, hydroxylation, oxidation to acid and glucuronidation

ND

1

(100)

M78

O-demethylated M77

ND

2

(200)

M79

Oxidation

ND

<1

(<100)

M80

Amide hydrolysis,
O-demethylation

ND

1

(100)

M81

N-dealkylation and hydroxylation

ND

<1

(<100)

aDetermined by 19F NMR integration.
ODRM = Observed Drug Related Material.
ND = Not Detected.
Table 2: Additional Minor Human Metabolites Identified in Pooled Plasma Extracts Following Single and Repeat Oral Administration of GSK1018921 to Healthy Volunteers.