Drug Metabolism in Drug Design and Development Basic Concepts and Practice

Carboxyl group

: clofibrate,

ciprofibrate, etodolac,fenoprofen, ibuprofen,ketoprofen, naproxen(racemic

>

S), valproic

acid and formation ofsimvastatin and atorvastatinlactones via an intermediateacyl glucuronide

UGT1A4

Estrogens:

2-hydroxy-estrone and 2-hydroxy

estradiol, 4-hydroxy catechol estrogens (low),estriol,

Progestins

:5

a-pregnan-3

a,20

a

-diol,

16

a

-hydroxy pregennolone, 19- hydroxy and

21- hydroxy pregnenolone, pregneneolone,androsterone, epiandrosterone, etiocholanone,Androgens:

dehydroepiandrosterone,

dihydrotestosterone, epitestosterone,testostereone, 5

a-androstan-3

a,17

b-diol,

5 b

-androstan-3

a,11

a,17

b-triol; bilirubin

(very low), F

-1 6

a,23S,25(OH)

D 3

 3

a

hexafluorinated Vit D

3

analog

Trifluoperazine:

6 m

M

(Ebner, 1993)

Hecogenin: 10

mM

(Uchaichipat, 2006;Green, 1998)

Tertiary amines:

amitriptyline,

chlorpheniramine,chlorpromazine,clozapine, cyproheptadine,diphenylamine, doxepin,imipramine, ketotifen,loxapine, promethazine,tripellenamine,trifluoperazine

Aromatic heterocyclic amines:

croconazole, lamotrigine,nicotine (30X velocity thanUGT1A3), 1-phenylimidazole,posaconazole, retigabine

phenobarbital,

phenytoin, andcarbamazepine

Primary and secondary amines

:

2- and 4-aminobiphenyl,diphenylamine,desmethylclozapine

Alcoholic and phenolic substrates:

borneol, carveol, carvacroldiosgenin,

hecogenin

,

isomenthol, menthol,neomenthol, 1- and 2-naphthol(low),

p-nitrophenol (low),

nopol, tigogenin

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