CYP3A4 Information & CYP3A4 Links at HealthHaven.com

Cytochrome P450, family 3, subfamily A, polypeptide 4
	; Structure of CYP3A4 (from PDB 1W0E).; Heme group visible at center.
Available structures
	1tqn, 1w0e, 1w0f, 1w0g, 2j0c, 2j0d
Identifiers
Symbols	CYP3A4; CYP3A; CP33; CP34; CYP3A3; HLP; MGC126680; NF-25; P450C3; P450PCN1
External IDs	OMIM: 124010 HomoloGene: 111391 GeneCards: CYP3A4 Gene
EC number	1.14.13.97
Gene ontology
Molecular function	• monooxygenase activity; • iron ion binding; • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; • oxygen binding; • heme binding; • metal ion binding; • unspecific monooxygenase activity; • quinine 3-monooxygenase activity; • testosterone 6-beta-hydroxylase activity;
Cellular component	• membrane fraction; • endoplasmic reticulum; • microsome; • cell surface; • membrane; • integral to membrane;
Biological process	• electron transport; • lipid metabolic process; • xenobiotic metabolic process;
RNA expression pattern
	More reference expression data
Orthologs

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Cytochrome P450 3A4 (abbreviated CYP3A4) (EC 1.14.13.97), a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. CYP3A4 is also, correspondingly, present in the largest quantity of all the CYPs in the liver.

Fetuses do not express CYP3A4 in their liver/tissues; but rather CYP3A7, which acts on a similar range of substrates. CYP3A4 is absent in fetal liver but increases to approximately 40% of adult levels in the first month of life.^[1]

**Selected inducers, inhibitors and substrates of CYP3A4^[2]**
Substrates	Inhibitors	Inducers
Often mentioned:^[3] calcium channel blockers diltiazem nifedipine felodipine amlodipine verapamil immunosuppressants ciclosporin tacrolimus sirolimus Chemotherapeutic cyclophosphamide docetaxel doxorubicin etoposide ifosfamide paclitaxel tamoxifen anastrazole teniposide vinblastine vindesine gefitinib benzodiazepines flunitrazepam midazolam alprazolam triazolam clonazepam azole antifungals ketoconazole itraconazole clotrimazole tricyclic antidepressants amitriptyline imipramine clomipramine macrolide erythromycin clarithromycin SSRIs citalopram escitalopram fluoxetine and norfluoxetine sertraline statins atorvastatin lovastatin simvastatin PDE5 inhibitors sildenafil buspirone (anxiolytic) haloperidol (antipsychotic) venlafaxine (SNRI) amiodarone (antiarrhythmic) ethinylestradiol (hormonal contraceptive) kinins (vasodilators, smooth muscle contractors) Other: protease inhibitors indinavir ritonavir saquinavir nelfinavir Mirtazapine (NaSSA) nefazodone (5-HT2A receptor antagonist) pimozide (antipsychotic) reboxetine (antidepressant) zopiclone (hypnotic) non-nucleoside reverse transcriptase inhibitors nevirapine alfentanil (analgesic) budesonide (glucocorticoid) donepezil (acetylcholinesterase inhibitor) esomeprazole (proton pump inhibitor) omeprazole (proton pump inhibitor) finasteride (antiandrogen) glibenclamide (antidiabetic) cisapride (5-HT4 receptor agonist) terfenadine (H1-receptor antagonist) toremifene (SERM) barbiturates phenobarbital carbamazepine (anticonvulsant, mood stabilizing) codeine (analgesic, antitussive, antidiarrheal) dextromethorphan (antitussive) digoxin (Antiarrhythmic) ergot alkaloids (circulation, neurotransmission) estradiol (sex hormone) fentanyl (analgesic) ivabradine (in angina pectoris) levonorgestrel (hormonal contraceptive) lidocaine (local anesthetic, antiarrhythmic) methadone (analgesic, anti-addictive) mifepristone (abortifacient) montelukast (leukotriene receptor antagonist) ondansetron (5-HT3 antagonist) paracetamol (analgesic, antipyretic) quinidine (class I antiarrhythmic) quinine (antipyretic, anti-smallpox, analgesic) testosterone (androgen) theophylline (stimulant) valproate (anticonvulsant, mood-stabilizing) warfarin (anticoagulant) tetrahydrocannabinol (psychoactive) Antipsychotics Aripiprazole Risperidone Ziprasidone	Strong/moderate:^[4]^[5] protease inhibitors ritonavir indinavir nelfinavir macrolide antibiotics erythromycin telithromycin clarithromycin azole antifungals fluconazole ketoconazole itraconazole nefazodone (5-HT2A receptor antagonist) bergamottin (constituent of grapefruit juice) quercetin aprepitant (Substance P antagonist, NK1 receptor antagonist) verapamil (calcium channel blocker) chloramphenicol (antibiotic)^[6] Weak:^[5] cimetidine (H2-receptor antagonist) unspecified:^[5] amiodarone (antiarrhythmic) ciprofloxacin (antibiotic) ciclosporin (immunosuppressant) diltiazem (calcium channel blocker) imatinib (anticancer) echinacea (immunostimulator) enoxacin (antibacterial) ergotamine (in migraine) metronidazole (antibacterial) mifepristone (abortifacient) norfloxacin (antibiotic) tofisopam (anxiolytic) non-nucleoside reverse transcriptase inhibitors ^[7] delavirdine efavirenz nevirapine gestodene (hormonal contraceptive) mibefradil (in angina pectoris) protease inhibitors saquinavir SSRIs fluoxetine/norfluoxetine fluvoxamine star fruit piperine	Often mentioned:^[3] barbiturates phenobarbital carbamazepine (anticonvulsant, mood stabilizing) oxcarbazepine non-nucleoside reverse transcriptase inhibitors ^[7] efavirenz nevirapine etravirine phenytoin (anticonvulsant) rifampicin (bactericidal) modafinil (stimulant) hyperforin (constituent of St Johns Wort) cyproterone (antiandrogen, progestin, Diane-35) Other: dexamethasone (anti-inflammatory, immunosuppressant) felbamate (anticonvulsant) glucocorticoids (blood glucose increase, immunosuppressive) griseofulvin (antifungal) pioglitazone (hypoglycemic) primidone (anticonvulsant) topiramate (anticonvulsant) troglitazone (hypoglycemic) rifabutin (in tuberculosis) cafestol (in unfiltered coffee)

[edit] References

^ Eve A. Roberts, M.D., FRCPC (2007). ""Drug Induced Liver Disease" - Chapter 20". Liver Disease In Children. Cambridge University Press. pp. 480. ISBN 10: 0521856574.
^ Where classes of agents are listed, there may be exceptions within the class
^ ^a ^b Mentioned both in the reference named FASS and were previously mentioned in Wikipedia. Further contributions may follow other systems
^ Swedish environmental classification of pharmaceuticals Facts for prescribers (Fakta för förskrivare)
^ ^a ^b ^c Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. http://medicine.iupui.edu/flockhart/table.htm. Retrieved on December 25, 2008.
^ Park JY, Kim KA, Kim SL (November 2003). "Chloramphenicol is a potent inhibitor of cytochrome P450 isoforms CYP2C19 and CYP3A4 in human liver microsomes". Antimicrob. Agents Chemother. 47 (11): 3464–9. PMID 14576103.
^ ^a ^b Non-nucleoside reverse transcriptase inhibitors have been shown to both induce and inhibit CYP3A4.

[edit] External links

PharmGKB: Annotated PGx Gene Information for CYP3A4

[0] Eve A. Roberts, M.D., FRCPC (2007). ""Drug Induced Liver Disease" - Chapter 20". Liver Disease In Children. Cambridge University Press. pp. 480. ISBN 10: 0521856574.

[1] Where classes of agents are listed, there may be exceptions within the class

[importance-2] Mentioned both in the reference named FASS and were previously mentioned in Wikipedia. Further contributions may follow other systems

[FASS-3] Swedish environmental classification of pharmaceuticals Facts for prescribers (Fakta för förskrivare)

[Flockhart-4] Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. http://medicine.iupui.edu/flockhart/table.htm. Retrieved on December 25, 2008.

[5] Park JY, Kim KA, Kim SL (November 2003). "Chloramphenicol is a potent inhibitor of cytochrome P450 isoforms CYP2C19 and CYP3A4 in human liver microsomes". Antimicrob. Agents Chemother. 47 (11): 3464–9. PMID 14576103.

[nnrti-6] Non-nucleoside reverse transcriptase inhibitors have been shown to both induce and inhibit CYP3A4.

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