Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 18.8 Structures of muraglitazar and its metabolites (M1, M2, M4, M4, M5).

Drug or metabolite Proposed structurea Source

Muraglitazar

O

N O N O

O O

HO

O

Rat: Plasma, urine, feces, bile

Dog: Plasma, urine, feces

Monkey: Plasma, urine,

feces, bile

Human: Plasma, urine,

feces, bile

M1
(O-Dealkyl
muraglitazar) HO
N O
O O

OH

O Rat: Plasma, urine, feces

Dog: Plasma, urine, feces

Monkey: Plasma, urine,

feces, bile

Human: Plasma, urine, feces

M2
(8-Hydroxy-
O-demethyl
muraglitazar) O

N O N O

O OH

OH

O

OH

Rat: Plasma, urine, feces, bile

Dog: NDb

Monkey: Plasma, urine,

feces, bile

Human: Plasma, urine,

feces, bile

M3
(8,12-Dihydroxy
muraglitazar)

O

N O

O O

OH

O

N

O

HO

OH

Rat: Urine

Dog: ND

Monkey: Feces, bile

Human: Plasma, urine, feces

M4
(9,12-Dihydroxy
muraglitazar)

O

N O

O O

OH

O

N

O

HO

HO

Rat: ND

Dog: Feces

Monkey: Feces, bile

Human: Plasma, urine, feces

M5
(12-Hydroxy-
O-demethyl
muraglitazar)

O

N O

NO

O OH

OH

O

OH

Rat: Plasma, urine, feces, bile

Dog: Plasma, urine, feces

Monkey: Plasma, urine,

feces, bile

Human: Plasma, urine,

feces, bile

aStructures were proposed based on MS data and comparison with synthetic metabolites.
bND = not detected.

In summary, for comparative biotransformation profiling, both quantitative
and qualitative metabolite profiles are important to understand the relative
abundance and identities of metabolites in various matrices from different
species. LC/MS and LC/MS/MS methods are complementary to quantitative
profiling using radioactivity detection when the existence of a metabolite needs

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