Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 3.3 Selective substrates for individual UGT1A isozymes.Isoenzyme Endogenous substrates

Reported

K

m

Drug or xenobiotic

substrates

Inducers

Inhibitors

UGT1A1

Bilirubin

,estradiol

(3-hydroxy),

2-hydroxyestrone,2-hydroxyestradioltrans-retinoic acid,catechol estrogens(2- and 4-hydroxy)

Ethinyl estradiol

, morphine

(3-hydroxy), buprenorphineferulic acid, genisteinnaltrexone (low),naloxone (low),SN-38 (active metaboliteof irinotecan) alizarin,quinalizarin

Bilirubin,

chlorophen-oxypropionicacid, chrysin,clofibrate3-methylcholanthrene,phenylpropionic acid,phenobarbital, etc.pregnenolone-16

a-

nitrile anddexamethasone,clotrimazole,rifampin,and St. John’s wort

Atazanavir

UGT1A2









UGT1A3 Bile acids (carboxyl

functional group),catechol estrogens(2-OH

>

4-OH),

2-OH-estrone,2-hydroxyestradiol,decanoic acid,dodecanoic acid,bilirubin (low)

Cyproheptadine

, alizarin,

buprenorphine

,

norbuprenorphine,bropirimine,diphenylamine,diprenorphine, emodin,esculetin, eugenol,ezetimibe, fisetin,genestein, 3-hydroxydesloratadine,7-hydroxyflavone, hydromorphone,4-methylumbelliferone, morphine,nalorphine, naloxone, naltrexone,naringenin

, quercehtin, scopoletin,

thymol, umbelliferone.

b-Naphthoflavone,

rifampin(?)

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