Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 3.4 Selective substrates for individual UGT2B isozymes.Isoenzyme

Endogenoussubstrates

Reported

Km

Drug or xenobiotic

substrates

Inducers

Inhibitors

UGT2B1

Estradiol

(17-hydroxy

)

Morphine

UGT2B2UGT2B3

Bile acids

UGT2B4 6

a

hydroxy bile acids, 3 a-hydroxy pregnanes, 3

a-,

16

a-, 17

b-androgens,

metabolites of polyunsaturated fattyacids (PUFA),arachidonic andlinoleic acids, estriol,2-hydroxy estriol,4-hydroxy estrone

Phenols:

Eugenol,4-nitrophenol,2-aminophenol,4-methyl umbelliferone,morphine

Fenofibric acid,

chenodeoxycholicacid-activatedFXR

UGT2B5UGT2B6UGT2B7

Arachidonic acid metabolites:

Leukotriene B4 (LTB4),5-hydroxyeicosatetraenoicacid (HETE), 12-HETE,15-HETE, and13-hydroxyoctadecadienoicacid (HODE)

R-Oxazepam

, naproxen,

menthol,

AZT (zidovudine)

,

abacavir, acetaminophen,almokalant, carvedilol,chloramphenicol,epirubicin, 1

0 -hydroxy

estragole, 5-hydroxyrofecoxib, lorazepam,menthol, 4-methylumbelliferone,1-naphthol (low), 4-nitrophenol,octylgallate, propranolol,temazepam, maxipost

Rifampin,

Phenobarbital,HNFHNF1

a

R-Oxazepam and

zidovudine (competitive),Flunitrazepam relativelypotent (

Ki



50–90

mM), but

also inhibits UGT1A3(K

= 20–30i

mM

for 2-hydroxy estrogens)and UGT1A1(K

>i

200

mM). diclofenac,

etonitazenyl

54