Reactions of aromatic hydroxylation

CYP isoform

Drug

Anatomical Therapeutic Chemical (ATC) Classification

Reaction*

Metabolites

Reference

CYP1A2

Melatonin

N05CH – Melatonin receptor agonists

6-hydroxylation

6-hydroxymelatonin

[5]

Mianserin

N06AX – Other antidepressants

8-hydroxylation

8-hydroxymianserin

[6]

Estradiol

G03CA – Natural and semisynthetic estrogens, plain

2-hydroxylation

2-hydroxyestradiol

[7]

CYP2A6

Efavirenz

J05AG – Non-nucleoside reverse transcriptase inhibitors

7-hydroxylation

7-hydroxyefavirenz

[8]

CYP2B6

Mianserin

N06AX – Other antidepressants

8-hydroxylation

8-hydroxymianserin

[6]

Propofol

N01AX – Other general anesthetics

4-hydroxylation

4-hydroxypropofol

[9]

Efavirenz

J05AG – Non-nucleoside reverse transcriptase inhibitors

8-hydroxylation

8-hydroxyefavirenz

[8]

CYP2C8

Rosiglitazone

A10BG – Thiazolidinediones

para-hydroxylation

para-hydroxyrosiglitazone

[10]

CYP2C9

Acenocoumarol

B01AA – Vitamin K antagonists

6- and 7-hydroxylation

6- or 7-hydroxyacenocoumarol

[11]

Diclofenac

S01BC – Antiinflammatory agents, non-steroids

4'-hydroxylation

4'-hydroxydiclofenac

[12]

Lornoxicam

M01AC – Oxicams

5'-hydroxylation

5'-hydroxylornoxicam

[13]

Piroxicam

M01AC – Oxicams

5'-hydroxylation

5'-hydroxypiroxicam

[14]

Phenytoin

N03AB – Hydantoin derivatives

4-hydroxylation

4-hydroxyphenytoin

[15]

Flurbiprofen

S01BC – Antiinflammatory agents, non-steroids

4'-hydroxylation

4'-hydroxyflurbiprofen

[16]

(S)-warfarin

B01AA – Vitamin K antagonists

7-hydroxylation

(S)-7-hydroxywarfarin

[17]

CYP2C19

Lansoprazole

A02BC – Proton pump inhibitors

5-hydroxylation

5-hydroxylansoprazole

[18]

Phenytoin

N03AB – Hydantoin derivatives

4-hydroxylation

4-hydroxyphenytoin

[15]

(R)-warfarin

B01AA – Vitamin K antagonists

8-hydroxylation

(R)-8-hydroxywarfarin

[19]

(S)-mephenytoin

N03AB – Hydantoin derivatives

4'-hydroxylation

(S)-4'-hydroxymephenytoin

[20]

CYP2D6

Aprindine

C01BB – Antiarrhythmics, class Ib

5-hydroxylation

5-hydroxyaprindine

[21]

Atomoxetine

N06BA – Centrally acting sympathomimetics

4-hydroxylation

4-hydroxyatomoxetine

[22]

Desipramine

N06AA – Non-selective monoamine reuptake inhibitors

2-hydroxylation

2-hydroxydesipramine

[23]

Duloxetine

N06AX – Other antidepressants

4-, 5- and 6-hydroxylation

4-, 5- or 6-hydroxyduloxetine

[24]

Imipramine

N06AA – Non-selective monoamine reuptake inhibitors

2-hydroxylation

2-hydroxyimipramine

[23]

Carvedilol

C07AG – Alpha and beta blocking agents

4'- and 5'-hydroxylation

4'- or 5'-hydroxycarvedilol

[25]

Quetiapine

N05AH – Diazepines, oxazepines, thiazepines and oxepines

7-hydroxylation

7-hydroxyquetiapine

[26]

Mianserin

N06AX – Other antidepressants

8-hydroxylation

8-hydroxymianserin

[27]

Mirtazapine

N06AX – Other antidepressants

8-hydroxylation

8-hydroxymirtazapine

[28]

Promethazine

R06AD – Phenothiazine derivatives

7-hydroxylation

7-hydroxypromethazine

[29]

Propafenone

C01BC – Antiarrhythmics, class Ic

5-hydroxylation

5-hydroxypropafenone

[30]

Propranolol

C07AA – Beta blocking agents, non-selective

4'- and 5'-hydroxylation

4'- or 5'-hydroxypropranolol

[31]

Tamoxifen

L02BA – Anti-estrogens

4-hydroxylation

4-hydroxytamoxifen

[32]

Chlorpromazine

N05AA – Phenothiazines with aliphatic side-chain

7-hydroxylation

7-hydroxychlorpromazine

[33]

(E)-clomifene

G03GB – Ovulation stimulants, synthetic

4-hydroxylation

4-hydroxyclomifene

[34]

CYP2E1

Chlorzoxazone

M03BB – Oxazol, thiazine, and triazine derivatives

6-hydroxylation

6-hydroxychlorzoxazone

[35]

CYP3A4/3A5

Atorvastatin

C10AA – HMG CoA reductase inhibitors

Para- and ortho-hydroxylation

Para- or ortho-hydroxyatorvastatin

[36]

Diclofenac

S01BC – Antiinflammatory agents, non-steroids

5-hydroxylation

5-hydroxydiclofenac

[37]

Quetiapine

N05AH – Diazepines, oxazepines, thiazepines and oxepines

7-hydroxylation

7-hydroxyquetiapine

[26]

Mianserin

N06AX – Other antidepressants

8-hydroxylation

8-hydroxymianserin

[6]

Nevirapine

J05AG – Non-nucleoside reverse transcriptase inhibitors

2-hydroxylation

2-hydroxynevirapine

[38]

Trazodone

N06AX – Other antidepressants

4'-hydroxylation

4'-hydroxytrazodone

[39]

Ethinylestradiol

L02AA – Estrogens

2-hydroxylation

2-hydroxythinylestradiol

[40]

Delakylation reactions

CYP1A2

Melatonin

N05CH – Melatonin receptor agonists

O-demethylation

N-acetylserotonin

[5]

Mianserin

N06AX – Other antidepressants

N-demethylation

N-desmethylmianserin

[6]

Naproxen

S01BC – Antiinflammatory agents, non-steroids

O-demethylation

O-desmethylnaproxen

[41]

Phenacetin

N02BE – Anilides

O-deethylation

O-deethylphenacetin (Acetaminophen, paracetamol)

[42]

CYP2C9

Indomethacin

S01BC – Antiinflammatory agents, non-steroids

O-demethylation

О-desmethylindomethacin

[43]

Carvedilol

C07AG – Alpha and beta blocking agents

O-demethylation

O-desmethylcarvedilol

[44]

CYP2C19

Melatonin

N05CH – Melatonin receptor agonists

O-demethylation

N-acetylserotonin

[5]

CYP2D6

Venlafaxine

N06AX – Other antidepressants

O-demethylation

О-desmethylvenlafaxine

[45]

Galantamine

N06DA – Anticholinesterases

O-demethylation

O-desmethylgalantamine

[46]

Gefitinib

L01XE – Protein kinase inhibitors

O-demethylation

O-desmethylgefitinib

[47]

Hydrocodone

R05DA – Opium alkaloids and derivatives

O-demethylation

O-desmethylhydrocodone

[48]

Dextromethorphan

R05DA – Opium alkaloids and derivatives

O-demethylation

Dextrorphan

[49]

Dihydrocodeine

N02AA – Natural opium alkaloids

O-demethylation

Dihydromorphine

[50]

Codeine

R05DA – Opium alkaloids and derivatives

O-demethylation

Morphine

[51]

Oxycodone

N02AA – Natural opium alkaloids

O-demethylation

O-desmethyloxycodone

[52]

Tramadol

N02AX – Other opioids

O-demethylation

O-desmethyltramadol

[53]

Flecainide

C01BC – Antiarrhythmics, class Ic

meta-O-dealkylation

meta-O-dealkylated flecainide

[54]

CYP2J2

Astemizole

R06AX — Other antihistamines for systemic use

O-demethylation

O-desmethylastemizole

[55]

CYP3A4/3A5

Donepezil

N06DA – Anticholinesterases

O-demethylation

O-desmethyldonepezil

[56]