cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
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Function
- NADPH-dependent electron transport pathway
- oxidizes a variety of structurally unrelated compounds, including
- steroids, fatty acids, xenobiotics
- metabolizes more drugs than any other P450 isozyme
- major P450 involved in activation of aflatoxin B1
- the R form of warfarin is a substrate of cyt P450 3A4
- inducers
- aminoglutethimide
- amprenavir
- aprepitant
- barbiturate
- carbamazepine
- dexamethasone
- efavirenz
- ethosuximide
- etravirine
- garlic
- glucocorticoid
- glutethimide
- griseofulvin
- modafinil
- nafcillin
- nevirapine
- oxcarbazepine
- phenobarbital
- phenytoin
- primidone
- rifabutin
- rifampin
- rifapentine
- ritonavir
- Hypericum perforatum (St John's wort)
- inhibitors
- acitretin
- amiodarone
- amprenavir
- aprepitant
- atazanavir
- Cannabis sativa
- chloramphenicol
- cimetidine
- ciprofloxacin*
- clarithromycin*
- cobicistat
- conivaptan
- cyclosporine
- danazol
- darunavir
- delavirdine
- diltiazem*
- dronedarone
- erythromycin*
- ethinyl estradiol
- everolimus
- fluconazole*
- fluoxetine
- fluvoxamine
- fosamprenavir
- galantamine
- grapefruit juice
- indinavir
- imatinib
- isoniazid
- itraconazole
- ketoconazole*
- lapatinib
- methylprednisolone
- mifepristone
- nefazodone
- nelfinavir
- nicardipine
- nifedipine
- norfloxacin
- Piper methysticum ;;(Kava-kava)
- pomegranate
- posaconazole
- Punica gratum (pomegranate)
- prednisone
- propoxyphene
- quinine
- ranolazine
- ritonavir
- saquinavir
- Synercid
- telithromycin
- tipranavir
- verapamil*
- voriconazole*
- zafirlukast
* common
- substrates
- alfuzosin
- aliskiren
- almotriptan
- alprazolam
- amitriptyline
- amiodarone
- amlodipine
- amprenavir
- aprepitant
- asenapine
- atazanavir
- atorvastatin
- beclomethasone
- bepridil
- bexarotene
- bosentan
- bromocriptine
- budesonide
- buprenorphine
- buspirone
- busulfan
- cannabinoid
- caffeine
- carbamazepine
- cevimeline
- chlorpheniramine
- ciclesonide
- cinacalcet
- cisapride
- citalopram
- clarithromycin
- clindamycin
- clomipramine
- clonazepam
- clopidogrel
- clozapine
- cocaine
- colchicine
- conivaptan
- cyclobenzaprine
- cyclophosphamide
- cyclosporine
- dapsone
- darifenacin
- darunavir
- dasatinib
- delavirdine
- desogestrel
- dexamethasone
- dextromethorphan
- diazepam
- dihydroergotamine
- dolasetron
- donepezil
- doxorubicin
- dronabinol
- dronedarone
- dutasteride
- efavirenz
- eplerenone
- ergotamine
- erlotinib
- erythromycin
- escitalopram
- esomeprazole
- estrogen
- eszopiclone
- ethinyl estradiol
- ethosuximide
- etonogestrel
- etoposide
- etravirine
- exemestane
- felodipine
- fentanyl
- fesoterodine
- fexofenadine
- finasteride
- flutamide
- fluticasone
- galantamine
- guanfacine
- haloperidol
- hydrocodone
- hydrocortisone
- ifosfamide
- iloperidone
- imatinib
- imipramine
- indinavir
- isradipine
- itraconazole
- ixabepilone
- ketoconazole
- lapatinib
- lansoprazole
- letrozole
- levobupivacaine
- lidocaine
- lopinavir
- loratadine
- losartan
- lovastatin
- maraviroc
- methadone
- methylprednisolone
- miconazole
- midazolam
- mifepristone
- mirtazapine
- modafinil
- mometasone
- montelukast
- nateglinide
- nefazodone
- nelfinavir
- nevirapine
- nicardipine
- nifedipine
- nilotinib
- nimodipine
- nisoldipine
- nitrendipine
- norethindrone
- omeprazole
- ondansetron
- oral contraceptive
- oxybutynin
- oxycodone
- paclitaxel
- pantoprazole
- pazopanib
- pimavanserin
- pimozide
- pioglitazone
- pravastatin
- prednisolone
- prednisone
- progesterone
- progestin
- propafenone
- propoxyphene
- quetiapine
- quinidine
- quinine
- rabeprazole
- ramelteon
- ranolazine
- repaglinide
- rifabutin
- rifampin
- ritonavir
- salmeterol
- saquinavir
- saxagliptin
- sertraline
- sibutramine
- sildenafil
- silodosin
- simvistatin
- sirolimus
- solifenacin
- sorafenib
- sunitimib
- tacrolimus
- tadalafil
- tamoxifen
- telithromycin
- temazepam
- testosterone
- tiagabine
- tinidazole
- tipranavir
- tolterodine
- tolvaptan
- toremifene
- tramadol
- trazodone
- triazolam
- trimetrexate
- ulipristal
- valdecoxib
- vardenafil
- verapamil
- vilazodone
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- warfarin
- zaleplon
- zileuton
- ziprasidone
- zolpidem
- zonisamide
Compartment
membrane-bound, endoplasmic reticulum
Expression
- expressed in liver & prostate
- induced by glucocorticoids
- induced to high levels in liver & other tissues by various foreign compounds, including drugs, pesticides, & carcinogens
- rifampin is a potent inducer of cyt P450 3A4
Laboratory
Notes
- efavirenz is both an inducer & an inhibitor of cyt P450 3A4
- ritonavir is a potent inhibitor of cyt P450 3A4
More general terms
Additional terms
- aflatoxin B1
- erythromycin (Eryc, Eryctte, E-mycin, Ilotycin, AK-Mycin, A/T/S, T-stat)
- ketoconazole (Nizoral, Xolegel)
- nifedipine (Procardia, Adalat)
References
- ↑ OMIM https://mirror.omim.org/entry/124010
- ↑ UniProt http://www.uniprot.org/uniprot/P08684.html
- ↑ Tarascon Pharmacopoeia, 2001
- ↑ Prescriber's Letter Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=150400&pb=PRL Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 11(4):24 2004
- ↑ Prescriber's Letter 11(6):31 2004 (telithromycin)
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Cytochrome P450 Allele Nomenclature committee, CYP3A4 alleles http://www.cypalleles.ki.se/cyp3a4.htm
- ↑ Wikipedia, CYP3A4 entry http://en.wikipedia.org/wiki/CYP3A4
- ↑ Prescriber's Letter 17(1): 2010 Cytochrome P450 Drug Interactions CHART: Cytochrome P450 Drug Interactions COMMENTARY: Proton Pump Inhibitor and Plavix Interaction: An Update Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260112&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 17(6): 2010 Cytochrome P450 Drug Interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260623&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 18(3): 2011 CHART: Cytochrome P450 Drug Interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=270307&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Spriet I, Meersseman W, de Hoon J et al Mini-series: II. clinical aspects. clinically relevant CYP450-mediated drug interactions in the ICU. Intensive Care Med. 2009 Apr;35(4):603-12 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19132344