A selected list of such interactions appears in the Table. Noni (M. citrifolia), for example, is a dietary supplement typically consumed as a juice and also inhibits CYP3A4;[24] pomegranate juice has this effect as well.[25]. Lovastatin (Mevacor) Estazolam (ProSom) [34] These analyses can be used as a high-sensitivity assay of drug binding, and may become integral in further high-throughput assays utilized in initial drug discovery testing. Although CYP3A4 is predominantly found in the liver, it is also present in other organs and tissues of the body, where it may play an important role in metabolism. Tadalafil (Cialis) Quinine Keywords: CYP3A4… Estimates of the turnover rate of human CYP3A4 vary widely. Zonisamide (Zonegran) Product Information: ORAVIG(R) buccal tablets, miconazole buccal tablets. Some drugs, such as clarithromycin, itraconazole, and ketoconazole, are particularly potent inhibitors of CYP3A4; patients on these drugs may have markedly reduced CYP3A4 activity. If use of strong CYP3A4/5 inhibitors is unavoidable, reduce the dose of axitinib by approximately half, as tolerated If use of strong CYP3A4/5 inducers is unavoidable, a gradual dose increase of axitinib is recommended, with patients carefully monitored for toxicity. Many drug interactions, therefore, involve additive effects of both CYP3A4 and P-glycoprotein. [11], Fetuses tend to not express CYP3A4 in their liver tissue,[clarification needed] but rather CYP3A7 (EC 1.14.14.1), which acts on a similar range of substrates. Modafinil Fluoxetine Bepridil (Vascor) a protein containing a heme group with an iron atom. Note: CYP3A4 is the main enzyme that metabolizes Gleevec and therefore effects may be more pronounced that those related to CYP2D6. Ethosuximide (Zarontin) The primary outcome occurred in 26.4% of patients in the DDI group and 18.4% in the control group (hazard ratio 1.8, 95% confidence interval [CI] 1.19 to 2.73; p-value = 0.006). Almotriptan (Axert) Lopinavir (Kaletra) Often this allows prodrugs to be activated and absorbed – as in the case of the histamine H1-receptor antagonist terfenadine. Oxycodone (Percodan) Bosentan (Tracleer) Bupropion (Zyban, Wellbutrin, Voxra) Cyclosporine The ERMBT estimates in vivo CYP3A4 activity by measuring the radiolabelled carbon dioxide exhaled after an intravenous dose of (14C-N-methyl)-erythromycin. Diltiazem Quazepam (Doral) Praelia Pharmaceuticals, Inc (per FDA), Cary, NC, 2013. Eplerenone (Inspra) Paclitaxel (Taxol) This type of drug interaction is probably more frequent than commonly realized, because reduced drug effect may simply be attributed to lack of patient response. Segen's Medical Dictionary. Prednisolone These include hydroxylation, epoxidation of olefins, aromatic oxidation, heteroatom oxidations, N- and O- dealkylation reactions, aldehyde oxidations, dehydrogenation reactions, and aromatase activity.[15][16]. [9] 20-HETE has a wide range of activities that also include growth stimulation in breast and other types of cancers (see 12-hydroxyeicosatetraenoic acid). The newer generation aromatase inhibitors (AIs) as a class show efficacy and tolerability benefits over previously established treatments inpostmenopausal women with advanced breast cancer. Gefitinib (Iressa) Bosentan [30] This effect has been attributed to CYP3A4 regulation by the growth hormone signal transduction pathway. inhibitors, such as diltiazem. It can be supposed that this may be due to the induction of CYP3A4 on exposure to substrates. A small number of drugs such as rifampin, phenytoin and ritonavir are identified as inducers of CYP3A4. Carbamazepine [18][19][20][21][22] In some cases, this can lead to a fatal interaction with drugs like astemizole or terfenadine. Propoxyphene (Darvon) Aprepitant [7] The EETs have a wide range of activities including the promotion of certain types of cancers (see epoxyeicosatetraenoic acid). Atazanavir (Reyataz) (on day 3 of 6 days of dosing), b fluconazole … Isoniazid Etoposide (Vepesid) Isradipine (DynaCirc) Ritonavir (Norvir) Testosterone Galantamine (Reminyl) Recently CYP3A4 has also been identified in the brain, however its role in the central nervous system is still unknown. By inhibiting CYP3A4, ritonavir increases plasma concentrations of other anti-HIV drugs oxidized by CYP3A4 thereby improving clinical efficacy. Sildenafil (Viagra) Activation of the PXR/RXR heterodimer initiates transcription of the CYP3A4 promoter region and gene. CYP3A4 localises to the endoplasmic reticulum; its expression is induced by glucocorticoids and drugs. Vomiting, headache, dizziness, drowsiness, Fever, diarrhea, muscle pain, paresthesias (may be fatal), Ergotism (peripheral ischemia, cyanosis, hypertension). Finasteride (Proscar) Co-crystallization is difficult since the substrates tend to have a low Kd (between 5-150 μM) and low solubility in aqueous solutions. Like all members of this family, it is a hemoprotein, i.e. © 2012 Farlex, Inc. Zolpidem (Ambien) [6] Most drugs undergo deactivation by CYP3A4, either directly or by facilitated excretion from the body. Midazolam (Versed) Loratadine (Claritin) Lapatinib Also, many substances are bioactivated by CYP3A4 to form their active compounds, and many protoxins being toxicated into their toxic forms (for examples – see table below). View chapter Purchase book 1tqn: Crystal Structure of Human Microsomal P450 3A4, 1w0e: CRYSTAL STRUCTURE OF HUMAN CYTOCHROME P450 3A4, 1w0f: CRYSTAL STRUCTURE OF HUMAN CYTOCHROME P450 3A4, 1w0g: CRYSTAL STRUCTURE OF HUMAN CYTOCHROME P450 3A4, 2j0d: CRYSTAL STRUCTURE OF HUMAN P450 3A4 IN COMPLEX WITH ERYTHROMYCIN. 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