Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 3.3 (

Continued

)

Isoenzyme

Endogenous substrates

Reported

Km

Drug or xenobiotic

substrates

Inducers

Inhibitors

2-hydroxy, 3- hydroxy,and 4- hydroxy biphenyl,buprenorphine (low),morphine (low), naloxone,naltrexone, ciprofibrate,diflunisal, diphenylamine,furosemide, mycophenolicacid (high), phenolphthalein,propofol, valproic acid,nandrolone, 1-methyl- 5 a

-androst-1-en-17

b-ol-

3-one (metabolite ofmetenolone), 5

a-androstane-

3 a

,17

b-diol (metabolite

of testosterone), (



)-

epigallocatechin gallate(tea phenol), SN-38(low)[metabolite of irinotecan],troglitazone (moderate), raloxifene(both 6

b- and 4

0 - b

-glucuronides),

querceten, luteolin

Entecapone: 10

mM

(Lautala, 2000)

UGT1A9/8

Retinoic acid,

thyroxine (T4),tri-iodothyronine(T3; minor),4-hydroxyestrone,4-hydroxyestradiol(major)

Planar phenols:

Phenol,

acetaminophen,2-hydroxybiphenyl,4-iodophenol,4-propylphenol,4-isopropylphenol(low), 4-ethylphenol,

TCDD,

tetrabutylhydroquinone,clofibric acid

High

concentrationsof propofol

50