The impact of such induction on CYP1A2 metabolic phenotype has been the subject of some discordant findings. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and paracetamol (acetaminophen). (f) Moderate inducer of CYP2B6, CYP2C19 and CYP3A. Note: Caution should be used when extrapolating the observed effect of ritonavir alone to the effect of combination regimens on CYP3A activities. It is reported that the estimated Ki value in inhibition studies tends to be lower. (d) Strong inhibitor of CYP2C8 and inhibitor of OATP1B1 and OAT3. Popular drugs that are metabolized, at least partially, by CYP1A2 include Wellbutrin, Zyprexa, and Cymbalta -- as well as … Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Inhibitors of CYP1A2 can be classified by their potency, such as: This article incorporates text from the United States National Library of Medicine, which is in the public domain. Food Effect and CYP1A2 Induction Study in Healthy Subjects Please note that Smart Patients does not conduct clinical trials. There are more than 50 CYP450 enzymes, but the CYP1A2, CYP2C19, CYP2D6, CYP1A2, CYP3A4, and CYP3A5 enzymes are responsible for metabolizing 45% of drug metabolism. (f) Usually administered to patients in combination with ritonavir, a strong CYP3A inhibitor. (2010), Hum Genomics, 5(1):61]. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. DrugFood interactions Caution w drugs that are inducers or inhibitors of CYP1A2 from NURSING 2361520162 at El Paso Community College Examples of in vitro inducers for P450-mediated metabolism (9/26/2016), Table 2-1: Examples of clinical index substrates for P450-mediated metabolism (for use in index clinical DDI studies) (9/26/2016). This table is prepared to provide examples of clinical inhibitors and is not intended to be an exhaustive list. (k) Also a substrate of OAT3. The CYP1A2 gene is responsible for the cytochrome P450 enzyme, which is responsible for liver detoxification and the metabolism of drugs. (h) Inhibitor of P-gp (defined as those increasing AUC of digoxin to ≥1.25-fold). (b) Strong inducer of CYP3A and moderate inducer of CYP1A2, CYP2C19. (f) Strong inhibitor of CYP2C19 and moderate inhibitor of CYP2C9 and CYP3A. (a) Strong inhibitor of CYP1A2 and CYP2C19, and moderate inhibitor of CYP2D6 and CYP3A. (g) Inhibitor of P-gp (defined as those increasing AUC of digoxin to ≥1.25-fold). **No selective inhibitor is available in vitro for CYP2C19- and CYP2B6-mediated metabolisms. Coffee consumption is a known inducer of cytochrome P450 1A2 (CYP1A2) enzyme activity. Cytochrome P450s CYP1A1 and CYP1A2 can metabolize a broad range of foreign compounds and drugs. Name Cytochrome P-450 CYP1A2 Inducers Accession Number DBCAT000614 (DBCAT004281) Description. Drug Interactions & Labeling, Recalls, Market Withdrawals and Safety Alerts, Drug Development and Drug Interactions: Possible Models for Decision-Making, Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers, Drug Development and Drug Interactions: Advisory Committee Meetings, Drug Interactions: Relevant Regulatory Guidance and Policy Documents, Preventable Adverse Drug Reactions: A Focus on Drug Interactions, and the list of references is available here, Phenacetin O-deethylation, 7-Ethoxyresorufin-O-deethylation, Efavirenz hydroxylation, Bupropion hydroxylation, Paclitaxel 6α-hydroxylation, Amodiaquine N-deethylation, S-Warfarin 7-hydroxylation, Diclofenac 4'-hydroxylation, Bufuralol 1'-hydroxylation, Dextromethorphan O-demethylation, Midazolam 1'-hydroxylation, Testosterone 6β-hydroxylation, Sertraline, Phencyclidine*, Thiotepa*, Ticlopidine*, S-(+)-N-3-benzyl-nirvanol, Nootkatone, Ticlopidine*, Itraconazole, Ketoconazole, Azamulin*, Troleandomycin*, Verapamil*, alosetron, caffeine, duloxetine, melatonin, ramelteon, tasimelteon, tizanidine, clozapine, pirfenidone, ramosetron, theophylline, glimepiride, phenytoin, tolbutamide, warfarin, atomoxetine, desipramine, dextromethorphan , eliglustat, encainide, imipramine, metoprolol, propafenone, propranolol, tramadol, trimipramine, S-venlafaxine, alfentanil, avanafil, buspirone, conivaptan, darifenacin, darunavir, budesonide, dasatinib, dronedarone, eletriptan, eplerenone, felodipine, indinavir, methoxsalen, mexiletine ,oral contraceptives, acyclovir, allopurinol, cimetidine, peginterferon alpha-2a, piperine, zileuton, diosmin, disulfiram, fluvastatin, fluvoxamine, abiraterone, cinacalcet, duloxetine, lorcaserin, mirabegron, amiodarone, celecoxib, cimetidine, clobazam, cobicistat, escitalopram, fluvoxamine, chlorzoxazone, cilostazol, cimetidine, clotrimazole, fosaprepitant, istradefylline, ivacaftor, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), Dabigatran etexilate, digoxin, fexofenadine, asunaprevir, atorvastatin, bosentan, danoprevir, docetaxel, amiodarone, carvedilol, clarithromycin, dronedarone, itraconazole, lapatinib, lopinavir and ritonavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, verapamil, atazanavir and ritonavir, clarithromycin, cyclosporine, erythromycin, gemfibrozil, lopinavir and ritonavir, rifampin (single dose), simeprevir, cimetidine, dolutegravir, isavuconazole, ranolazine, trimethoprim, vandetanib, Examples of clinical substrates, inhibitors, and inducers, Examples of clinical substrates, inhibitors and inducers. Cytochrome 1A2 (CYP1A2) 4 accounts for 13% of the total hepatic content of cytochrome isoenzymes and plays a role in the metabolism of various drugs, such as clozapine, olanzapine, omeprazole, erythromycin, propranolol, and paracetamol (1, 2). Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. little contribution of CYP1A2 (16, 17). Criteria for selecting in vivo inhibitors are as follows: This table is prepared to provide examples of clinical inhibitors for various transporters and not intended to be an exhaustive list. Some Enzymes and Selected Substrates (c)Listed based on pharmacogenetic studies. Table 4-1: Examples of in vitro substrates for transporters (9/26/2016). (d) Also an inhibitor of OCTs. (a) We currently do not have sensitive index substrates for CYP2B6. John's wort and common valerian were the strongest inducing herbs. If you would like to enroll in a trial or if you need more information please contact the trial team directly. (2010), Hum Genomics, 5(1):61], and the list of references is available here. In addition to induction of CYP3A4 by St. John's wort, common valerian and Ginkgo biloba increased the activity of CYP3A4 and 2D6 and CYP1A2 and 2D6, respectively. Guideline on the Investigation of Drug Interactions. Cytochrome P-450 1A2 (CYP1A2) is a biotransformation enzyme that activates several procarcinogens. See section IV.A.2. (e) Sensitive substrate of CYP2D6 and moderate sensitive substrate of CYP3A. Moderate sensitive substrates are drugs that demonstrate an increase in AUC of ≥2 to <5-fold with strong index inhibitors of a given metabolic pathway in clinical DDI studies. AhR-mediated induction by smoking or food components can markedly increase CYP1A2 activity. CYP1A2 is induced by cruciferous and inhibited by apiaceous vegetable intake. (a) Strong inducer of CYP1A2, CYP2C19, CYP3A, and moderate inducer of CYP2B6, CYP2C8, CYP2C9. Using a randomized, crossover feeding trial in humans, we investigated the dose effects of cruciferous vegetables and the effects of any interaction between cruciferous and apiaceous vegetables on CYP1A2 activity. (b)In vivo data suggested specific inhibition of OAT1. BCRP: (1) AUC fold-increase≥2 with pharmacogenetic alteration of ABCG2 (421C>A) and (2) in vitro transport by BCRP expression systems. CYP2C9 substrates-warfarin-S-phenytoin-NSAIDs-ARBs-sulfonylureas. (2010), Hum Genomics, 5(1):61]. P-gp: (1) AUC fold-increase≥2 with verapamil or quinidine co-administration and (2) in vitro transport by P-gp expression systems, but not extensively metabolized. (d) S-lansoprazole is a sensitive substrate in CYP2C19 EM subjects. The selectivity and potency of inhibitors should be verified in the same experimental conditions using probe substrates for each CYP enzyme. 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