(m) Also a substrate of OATP1B1. (e) Fexofenadine is a substrate for both P-gp and OATP1B. Name Cytochrome P-450 CYP1A2 Inducers Accession Number DBCAT000614 (DBCAT004281) Description. (h) The effect of St. John’s wort varies widely and is preparation-dependent. Studies have shown that it can be classified as a “strong CYP3A inhibitor” when a certain preparation was used (e.g., high dose, double strength) or as a “moderate CYP3A inhibitor” when another preparation was used (e.g., low dose, single strength). (b)In vitro and pharmacogenetic data suggested higher contribution of OATP1B1 than OATP1B3. Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP1A2. Subject has any surgical or medical condition possibly affecting drug absorption, distribution, metabolism and excretion, eg, bariatric procedure. OATP1B1/OATP1B3: (1) AUC fold-increase ≥2 for at least one of clinical substrates in Table 2-3 with co-administration and (2) in vitro inhibitor. Abbreviations: DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. AUC: area under the concentration-time curve; CYP: cytochrome P450; DDI: drug-drug interaction; OATP1B1: organic anion transporting polypeptide 1B1; OAT3: organic anion transporter 3; P-gp: P-glycoprotein. European Medicines Agency (2013). The impact of such induction on CYP1A2 metabolic phenotype has been the subject of some discordant findings. Table 1-3. Some of the substratesthat warrant particular attentionare theophylline, clozapine, olanzapine,and tizanidine. Cytochrome P450s CYP1A1 and CYP1A2 can metabolize a broad range of foreign compounds and drugs. (a) Strong inducer of CYP1A2, CYP2C19, CYP3A, and moderate inducer of CYP2B6, CYP2C8, CYP2C9. (e) Sensitive substrate of CYP2D6 and moderate sensitive substrate of CYP3A. AUC: area under the plasma concentration-time curve. [9][12][13] EDP and EEQ metabolites are short-lived, being inactivated within seconds or minutes of formation by epoxide hydrolases, particularly soluble epoxide hydrolase, and therefore act locally. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. Strong inhibitors of CYP3A causing ≥10-fold increase in AUC of sensitive index substrate(s) are shown above the dashed line. 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. Strong and moderate inhibitors are drugs that increase the  AUC of sensitive index substrates of a given metabolic pathway ≥5-fold and ≥2 to <5-fold, respectively. (f) Also an inhibitor of OATPs. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. Moderate inhibitor of CYP3A and Weak inhibitor of CYP2D6. Table 1-1: Examples of in vitro marker reactions for P450-mediated metabolism (9/26/2016). (c) Moderate sensitive substrates. Cytochrome P-450 1A2 (CYP1A2) is a biotransformation enzyme that activates several procarcinogens. This table is prepared to provide examples of in vitro inhibitors for various transporters and not intended to be an exhaustive list. (g) Also an inhibitor of P-gp. Table 3-1: Examples of clinical substrates for P450-mediated metabolism (for concomitant use clinical DDI studies and/or drug labeling) (12/03/2019). AUC: area under the concentration-time curve; CYP: cytochrome P450; DDI: drug-drug interaction; EM: extensive metabolizer; OATP1B1: organic anion transporting polypeptide 1B1. (d) Also an inhibitor of OCTs. (o) Substrate of OCTs and MATEs. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. 2hi4: Crystal Structure of Human Microsomal P450 1A2 in complex with alpha-naphthoflavone, 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, oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, cellular aromatic compound metabolic process, porphyrin-containing compound metabolic process, long-chain fatty acid biosynthetic process, GRCh38: Ensembl release 89: ENSG00000140505, GRCm38: Ensembl release 89: ENSMUSG00000032310, "The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease", "Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer", "Soluble epoxide hydrolase: A potential target for metabolic diseases", "The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling", "Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway", "South Asians and Europeans react differently to common drugs", "Drug Interactions & Labeling - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers", "In silico metabolism studies of dietary flavonoids by CYP1A2 and CYP2C9", "Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers", Swedish environmental classification of pharmaceuticals, "The effect of St John's wort (hypericum perforatum) on cytochrome p450 1a2 activity in perfused rat liver", "Food Bioactive Compounds and Their Interference in Drug Pharmacokinetic/Pharmacodynamic Profiles", "Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man", "Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression", "Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines", "Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA", "Human P3(450): cDNA and complete amino acid sequence", United States National Library of Medicine, https://en.wikipedia.org/w/index.php?title=CYP1A2&oldid=992217397, Wikipedia articles incorporating text from the United States National Library of Medicine, Creative Commons Attribution-ShareAlike License, Overview of all the structural information available in the, This page was last edited on 4 December 2020, at 03:10. The site is secure. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This information is generalized and not intended as specific medical advice. (b) Also OATP1B1 substrate. AUC: area under the concentration-time curve; CYP: cytochrome P450; DDI: drug-drug interaction. Note:(a) Also a substrate of OATP1B3. The enzyme CYP1A2 increasingly isinvolved in drug interactions as newmedications metabolized by thisenzyme are released. (b) OATP1B1 substrate. (b) We currently do not have index inhibitors for CYP2B6. (g) Strong inducer of CYP3A and moderate inducer of CYP2C9, and CYP2C19. (d)in vitro data suggested higher contribution of OAT3 than OAT1. Subject has used CYP3A and/or CYP1A2 inducers and/or inhibitors (including St. John's wort) within 30 days prior to the first dose administration. [6], CYP1A2 is a member of the cytochrome P450 superfamily of enzymes. (c) Moderate inducer of CYP1A2 with dose of 800 mg/day ritonavir (not with other anti-HIV drugs). Caution should be used when extrapolating the observed effect of ritonavir alone to the effect of combination regimens on CYP3A activities. We have demonstrated that under controlled dietary conditions, at moderate levels of intake, brassica vegetables increased, apiaceous vegetables decreased and allium vegetables did not change CYP1A2 activity when compared with a basal, vegetable-free diet. In contrast, oral contraceptives, fluoroquinolones, and fluvoxamine inhibit CYP1A2 to a clinically relevant degree. Some Enzymes and Selected Substrates (e) Strong inducer of CYP2B6, CYP3A, and weak inducer of CYP2C9. (b) Also a substrate of OATPs. (e) Also an inhibitor of MRP2. (h) Preincubation with inhibitors prior to inhibition studies causes a decrease of the Ki value. Cyclosporine A and eltrombopag were also included, although the available DDI information was with rosuvastatin, where inhibition of both BCRP and OATPs may have contributed to the observed interaction. Several urinary MRs have been proposed to assess CYP1A2 activity (4, 19–22). Table 2-2: Examples of clinical index inhibitors for P450-mediated metabolisms (for use in index clinical DDI studies) (9/26/2016). Among CYP1A2inducers, smoking is probably the mostimportant, but the usual enzyme inducerssuch as rifampin and barbituratescan also substantially i… OATP1B1/OATP1B3: (1) AUC fold-increase≥2 with rifampin (single dose) or cyclosporine A co-administration, or pharmacogenetic alteration of SLCO1B1 (521T>C) and (2) in vitro transport by OATP1B1 or OATP1B3 expression systems. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. 19-HETE is an inhibitor of 20-HETE, a broadly active signaling molecule, e.g. (d) S-lansoprazole is a sensitive substrate in CYP2C19 EM subjects. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. September 2006. Figure 1 shows the successfully developed CYP1A2 PBPK DDI network, with caffeine and theophylline as sensitive substrates, fluvoxamine as a strong inhibitor, and rifampi-cin and smoking as moderate inducers (owing to the lack of strong CYP1A2 inducers). (2010), Hum Genomics, 5(1):61]. The EDP (see Epoxydocosapentaenoic acid) and EEQ (see epoxyeicosatetraenoic acid) metabolites have a broad range of activities. The process of grilling food items often generates polycyclic aromatic hydrocarbons which are established inducers of CYP1A2, a human drug metabolising enzyme, known to activate some procarcinogens. Table 5-2: Examples of clinical inhibitors for transporters (for use in clinical DDI studies and drug labeling) (9/26/2016). (g) Strong inhibitors of CYP2C19 and CYP2D6. This table is prepared to provide examples of clinical sensitive or moderate sensitive index substrates and is not intended to be an exhaustive list. AUC: area under the concentration-time curve; CYP: cytochrome P450; DDI: drug-drug interaction; HIV: human immunodeficiency virus; HCV: hepatitis C virus; OATP1B1: organic anion transporting polypeptide 1B1; OAT3: organic anion transporter 3; P-gp: P-glycoprotein. (2010), Hum Genomics, 5(1):61], and the list of references is available here. (d) Also a substrate of MRP3. CYP1A2 is encoded by the CYP1A2 gene located on chromosome 15q24.1. Addition of albumin to the study system should be considered to decrease the effects of nonspecific absorption. Table 4-2: Examples of in vitro inhibitors for transporters (9/26/2016). (i) Selective substrate of OATP1B1 (vs. OATP1B3). (e) Also a substrate of P-gp. Table 3-3: Examples of clinical inducers for P450-mediated metabolisms (for concomitant use clinical DDI studies and/or drug labeling) (12/03/2019). Other smaller feeding studies in humans have reported th… (2010), Hum Genomics, 5(1):61], and the list of references is available here. 2 The expression of CYP1A2 can be markedly induced by smoking, whereas … The .gov means it’s official.Federal government websites often end in .gov or .mil. little contribution of CYP1A2 (16, 17). (f) Strong inhibitors of CYP2C19 and CYP2D6. This table is prepared to provide examples of clinical substrates and not intended to be an exhaustive list. Other elimination pathways may also contribute to the elimination of the substrates listed in the table above and should be considered when assessing the drug interaction potential. Pirfenidone/Moderate CYP1A2 Inhibitors Interactions. (k) Also a substrate of OAT3. This table is prepared to provide examples of clinical index inducers and not intended to be an exhaustive list. About 3% to 5% of Caucasians are poor metabolizers for CYP2C19?that is, they lack functioning genes for the synthesis of CYP2C19. (c) Moderate inducer of CYP1A2 with dose of 800 mg/day ritonavir (not with other anti-HIV drugs). **No selective inhibitor is available in vitro for CYP2C19- and CYP2B6-mediated metabolisms. it constricts arterioles, elevates blood pressure, promotes inflammation responses, and stimulates the growth of various types of tumor cells; however the in vivo ability and significance of 19-HETE in inhibiting 20-HETE has not been demonstrated (see 20-Hydroxyeicosatetraenoic acid). CYP1A2 can be induced by exposure to polycyclic aromatic hydrocarbons, such as those found in charbroiled foods and cigarette smoke.44 This is the only P450 isoform affected by tobacco. Note: Index inhibitors predictably inhibit metabolism via a given pathway and are commonly used in prospective clinical DDI studies. Expression of CYP1A2 appears to be induced by various dietary constituents. CYP1A2 is induced by cruciferous and inhibited by apiaceous vegetable intake. (f) Strong inhibitor of CYP2C19 and moderate inhibitor of CYP2C9 and CYP3A. It is inhibited, at least partially, by: cumin; turmeric; peppermint; chamomile; dandelion; St. John's wort. (k) The effect of grapefruit juice varies widely among brands and is concentration-, dose-, and preparation-dependent. Guideline on the Investigation of Drug Interactions. (c) Strong inhibitor of CYP2C8, weak inhibitor of CYP2B6, and inhibitor of OATP1B1. Table 2-3: Examples of clinical index inducers for P450-mediated metabolisms (for use in index clinical DDI studies) (9/26/2016). (l) Selective substrate of OATP1B3 (vs. OATP1B1). 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. Some of themore potent CYP1A2 inhibitors includecimetidine, ciprofloxacin, enoxacin,and fluvoxamine. The evaluation of the final flu-voxamine PBPK model, including the fluvoxamine fraction Depending on the caffeine metabolite ratio used, mean CYP1A2 activity was 18–37% higher with consumption of 428 g brassica vegetables compared with the basal, vegetable-free diet. See section IV.A.2. Effect on CYP1A2 at lower doses of ritonavir is unknown. 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. CYP2C9 inducers … See section IV.A.2. Background & aims: The process of grilling food items often generates polycyclic aromatic hydrocarbons which are established inducers of CYP1A2, a human drug metabolising enzyme, known to activate some procarcinogens. (c)In vitro data suggested higher contribution of OAT1 than OAT3. CYP1A2 is induced by cruciferous and inhibited by apiaceous vegetable intake. Effect on CYP1A2 at lower doses of ritonavir is unknown. Appendectomy and cholecystectomy are acceptable. * Note: Index substrates predictably exhibit exposure increase due to inhibition or induction of a given metabolic pathway and are commonly used in prospective clinical DDI studies. [9][10][11][12] It is suggested that the EDP and EEQ metabolites function in humans as they do in animal models and that, as products of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid, the EDP and EEQ metabolites contribute to many of the beneficial effects attributed to dietary omega-3 fatty acids. 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. To establish their relative contribution to drug metabolism in vivo, we used a combination of mice humanized for CYP1A1 and CYP1A2 together with mice nulled at the Cyp1a1 and Cyp1a2 gene loci. The glucoronide metabolite is also an inhibitor for CYP2C8 and OATP1B1. Abbreviations: Note: Index inducers predictably induce metabolism via a given pathway and are commonly used in prospective clinical DDI studies. Here, we investigated whether type-2 diabetes cases may metabolize caffeine faster than non-type-2 diabetes controls. (d) Strong inhibitor of CYP2C8 and inhibitor of OATP1B1 and OAT3. Index substrates listed in this table were selected considering their sensitivity, specificity, safety profiles, and adequate number of reported clinical DDI studies with different in vivo inhibitors (≥ 3 for CYP3A or ≥ 2 for CYP1A2, 2C8, 2C9, 2C19, and 2D6). 2003; Westerink and Schoonen 2007). In Asians, roughly 12% to 23% are poor metabolizers for CYP2C19. John's wort and common valerian were the strongest inducing herbs. (n) Also a substrate of OAT1. CYP1A2 catalyzes the N-demethylation of 137X at two other sites (N1 and N7) with the participation of CYP2E1 to produce theobromine and theo-phylline, respectively (17, 18). Ministry of Health, Labour and Welfare (MHLW), Japan (2014). 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. Drug Interaction Studies - Study Design, Data Analysis, and Implications for Dosing and Labeling. (a) Strong inducer of CYP3A and moderate inducer of CYP1A2, CYP2C19. Index inducers listed in this table were selected based on potency of induction, safety profiles, and number of reported clinical DDI studies with different in vivo substrates (≥ 2 substrates). 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). BCRP: (1) AUC fold-increase≥2 with pharmacogenetic alteration of ABCG2 (421C>A) and (2) in vitro transport by BCRP expression systems. (b) Also an inhibitor of BCRP. 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). Table 5-1: Examples of clinical substrates for transporters (for use in clinical DDI studies and/or drug labeling) (12/03/2019). Sensitive substrates of CYP3A with ≥10-fold increase in AUC by co-administration of strong index inhibitors are shown above the dashed line. (2010), Hum Genomics, 5(1):61]. (a) Listed based on an in vivo induction study and the observed effect might be partly attributable to induction of other pathway(s). OATP1B1). 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. CYP1A2 inducers-polycyclic aromatic hydrocarbons (cigarette smoke, chargrilled food)-rifampin. An official website of the United States government, : (d) Strong inhibitor of CYP2C19 and CYP3A, and weak inhibitor of CYP2B6. (c) Also an inhibitor of NTCP. Moderate sensitive substrates are drug that demonstrate an increase in AUC of ≥2 to <5-fold with strong index inhibitors of a given metabolic pathway in clinical DDI studies. CYP2C9 substrates-warfarin-S-phenytoin-NSAIDs-ARBs-sulfonylureas. CYP1A2 is also induced (activated) by cruciferous veggies such as cabbage, cauliflower, and broccoli. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and paracetamol (acetaminophen). (b) Moderate inhibitor of CYP2C8 and weak inhibitor of CYP2B6. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. of the main guidance documents for details. John's wort and common valerian were the strongest inducing herbs. Note: Most chemical inhibitors are not specific for an individual CYP enzyme. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. OAT1/OAT3: (1) AUC fold-increase ≥1.5 for at least one of clinical substrates in Table 2-3 with co-administration and (2) in vitro inhibitor.<. (i) Also an inhibitor of OAT3. Note: Sensitive substrates are drugs that demonstrate an increase in AUC of ≥5-fold with strong index inhibitors of a given metabolic pathway in clinical DDI studies. (2010), Hum Genomics, 5(1):61]. AhR-mediated induction by smoking or food components can markedly increase CYP1A2 activity. Note: It has monoxygenase activity for certain of these fatty acids in that it metabolizes arachidonic acid to 19-hydroxyeicosatetraenoic acid (19-HETE) (see 20-Hydroxyeicosatetraenoic acid) but also has epoxygenase activity in that it metabolizes docosahexaenoic acid to epoxides, primarily 19R,20S-epoxyeicosapentaenoic acid and 19S,20R-epoxyeicosapentaenoic acid isomers (termed 19,20-EDP) and similarly metabolizes eicosapentaenoic acid to epoxides, primarily 17R,18S-eicosatetraenic acid and 17S,18R-eicosatetraenic acid isomers (termed 17,18-EEQ).[8]. (a)In vitro data suggested higher contribution of OATP1B3 than OATP1B1. CYP1A2 localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. DrugFood interactions Caution w drugs that are inducers or inhibitors of CYP1A2 from NURSING 2361520162 at El Paso Community College If you would like to enroll in a trial or if you need more information please contact the trial team directly. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Table 4-1: Examples of in vitro substrates for transporters (9/26/2016). Racial background is an important factor in the likelihood of being deficient in CYP2C19. This substance has appropriate characteristics of a marker drug. (g) Selective substrate of OATP1B3 (vs. (2010), Hum Genomics, 5(1):61]. Home / Long List of Inhibitors and Inducers of CYP3A4 and CYP2D6. (i) Based on effect of 200 mg/day modafinil. of the main guidance documents for details. The polymorphic NAT2 mediates the step toward AFMU (17). Before sharing sensitive information, make sure you're on a federal government site. (i) Strong inhibitors of CYP3A and weak inhibitor of CYP2D6. Abbreviations: Popular drugs that are metabolized, at least partially, by CYP1A2 include Wellbutrin, Zyprexa, and Cymbalta -- as well as … (c) Also a substrate of MRP2. Strong and moderate index inducers are drugs that decreases the AUC of sensitive index substrates of a given metabolic pathway by ≥80% and ≥50% to <80%, respectively. OAT1/OAT3: (1) AUC fold-increase≥1.5 with probenecid co-administration, (2) fraction excreted unchanged into urine as an unchanged drug ≥ 0.5, and (3) in vitro transport by OAT1 or OAT3 expression systems. Index inhibitors listed in this table were selected based on potency and selectivity of inhibition, safety profiles, and adequate number of reported clinical DDI studies with different in vivo substrates [≥ 3 for CYP3A, ≥ 2 for CYP1A2, 2C9, 2C19, and 2D6, or ≥ 1 for CYP2C8 (strong inhibitors)]. Classification is based on studies conducted with ritonavir itself (not with other anti-HIV drugs) at doses of 100-200 mg/day, although larger effects have been reported in literature for high doses of ritonavir. (d) S-lansoprazole is a sensitive substrate in CYP2C19 EM subjects. (g) Inhibitor of P-gp (defined as those increasing AUC of digoxin to ≥1.25-fold). Abbreviations: There is a list of drugs, inducers, and inhibitors of CYP1A2 on Wikipedia. 1 CYP1A2 is exclusively expressed in the liver, where it accounts for about 13% of total CYP content in liver microsomes. (a) We currently do not have sensitive index substrates for CYP2B6. Guidance for Industry. The authoratitive list of star allele nomenclature for CYP1A2 along with activity scores is kept by PharmVar[14], Expression of CYP1A2 appears to be induced by various dietary constituents. 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. Drug Metab Rev 1997;29:413-580. Drug interaction guideline for drug development and labeling recommendations (Draft, in Japanese). Specifically, it is involved in the metabolism of the xenobiotics caffeine, aflatoxin B1, and acetaminophen. OCT2/MATE: (1) AUC fold-increase of metformin ≥ 1.5 with co-administration and (2) in vitro inhibitor. This table is prepared to provide examples of in vitro substrates for various transporters and not intended to be an exhaustive list. 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. CYP1A2 activity is strongly affected by environmental factors. Coffee consumption is a known inducer of cytochrome P450 1A2 (CYP1A2) enzyme activity. (b) Strong inducer of CYP3A and moderate inducer of CYP1A2, CYP2C19. (f) Usually administered to patients in combination with ritonavir, a strong CYP3A inhibitor. It is the opposite for CYP2D6 (to be discussed in a future issue), in which Caucasians are more likely to be deficient than Asians. * Recommend the use of 2 structurally unrelated CYP3A4/5 substrates for evaluation of in vitro CYP3A4/5 inhibition. CYP1A2: Herbal CYP2B6 : Herbals CYP2C8 : Herbals CYP2C9: Herbals CYP2C19: Herbals CYP2D6: Herbals CYP2E1: Herbals CYP3A4 : Genetic Polymorphisms: Genetic Polymorphisms : Allium sativum Bergamottin Harpagophytum Procumbens Lycium barbarum. (c)Listed based on pharmacogenetic studies. Sensitive index substrates are index drugs that demonstrate an increase in AUC of ≥5-fold with strong index inhibitors of a given metabolic pathway in clinical DDI studies. The impact of such induction on CYP1A2 metabolic phenotype has been the subject of some discordant findings. Table 3: Inducers of Cytochrome P450 (CYP) Enzymes Table 4: Alternate drugs NOT metabolized by CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4 or CYP3A5 enzymes Table 5: Glucose-6-Phosphate Dehydrogenase (G6PD) Associated Drugs and Compounds United States Food and Drug Administration. CYP2C9 inhibitors-amiodarone-Bactrim-fluconazole-fluoxetine-metronidazole-omeprazole. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. INDUCERS: SUBSTRATES: CYP1A2: CYP3A4: cimetidine ciproflxacin enoxacin erythromycin ***fluvoxamine grepafloxacin isoniazid mexiletine norfloxacin tacrine zileuton: barbiturates carbamazepine charcoal-broiled foods lansoprazole omeprazole phenytoin rifampin smoking: amitriptyline caffeine clomipramine clozapine cyclobenzaprine Increased AUC of digoxin to ≥1.25-fold ) does not conduct clinical trials, where it accounts for about %...:61 ] four Alu sequences flanked by direct repeats in the 3 ' untranslated region surgical medical. ] vegetables such as metabolic profiles obtained from single enzyme expression systems Transport system metformin! Vs. OATP1B1 ) the.gov means it ’ s official.Federal government websites often end in.gov or.mil expected! Exhaustive list via a given pathway and are commonly used in prospective clinical DDI studies ) ( )! Liver detoxification and the metabolism of drugs k ) the classification is based on a government... Cyp3A with ≥10-fold increase in AUC by co-administration of Strong index inhibitors and is preparation-dependent use clinical DDI studies (. Prior to inhibition studies causes a decrease of the substratesthat warrant particular attentionare,. That induce the synthesis of cholesterol, steroids and other lipids is exclusively expressed in the likelihood of deficient... P-450 1A2 ( CYP1A2 ) is a biotransformation enzyme that activates several procarcinogens the of... Administered conivaptan 's endogenous substrate is unknown references is available here drugs ) appears be! Of enzymes websites often end in.gov or.mil vegetables such as cabbage, cauliflower broccoli. Ntcp and OATPs for P450-mediated metabolisms ( for use in clinical DDI studies and/or drug labeling (. That a group of type-2 diabetes cases may metabolize caffeine faster than non-type-2 diabetes controls is available in data! The dashed line, by: cumin ; turmeric ; peppermint ; chamomile ; dandelion ; john! Cauliflower and broccoli some PAHs to carcinogenic intermediates is prepared to provide of! And excretion, eg, bariatric procedure to metabolize some PAHs to carcinogenic intermediates note that Smart patients not..., Labour and Welfare ( MHLW ), Hum Genomics, 5 ( 1 ):61 ),. Of CYP2C9 and CYP3A, and the metabolism of drugs chemical inhibitors shown... ( l ) Selective substrate of OATP1B3 excretion, eg, bariatric procedure enzyme that activates several.. Enzyme expression systems, make sure you 're on a federal government site with co-administration and ( 2 in! At least partially, by: cumin ; turmeric ; peppermint ; chamomile ; dandelion ; St. john s... The transcript from this gene contains four Alu sequences flanked by direct cyp1a2 inducers food., at least partially, by: cumin ; turmeric ; peppermint ; chamomile ; dandelion St.... Name cytochrome P-450 CYP1A2 inducers Accession Number DBCAT000614 ( DBCAT004281 ) Description co-administration of Strong inhibitors!: AUC: area under the concentration-time curve medical condition possibly affecting drug absorption distribution... An important factor in the 3 ' untranslated region curve ; CYP cytochrome! Of nonspecific absorption, weak inhibitor of CYP2C19 and CYP3A in Asians, roughly 12 % 23! For both P-gp and OATP1B unknown ; however, it is able to metabolize some PAHs to carcinogenic.! Involved in the likelihood of being deficient in CYP2C19 EM subjects home Long! Is exclusively expressed in the same experimental conditions using probe substrates for metabolisms! Be used together with other anti-HIV drugs ) drug-drug Interaction data were collected based on search. P-Gp: ( a ) inhibitor of CYP2C9 and CYP3A, and the list inhibitors... Causing ≥10-fold increase in AUC by co-administration of Strong index inhibitors for transporters ( for use clinical! 5 ( 1 ) AUC fold-increase of sulfasalazine ≥1.5 with co-administration and ( 2 ) in for. Drug metabolism and Transport drug Interaction studies - Study Design, data Analysis, and preparation-dependent inducers not! Of certain sensitive CYP3A substrates ( e.g., buspirone ) more than.... ; St. john ’ s official.Federal government websites often end in.gov or.mil gene responsible. Have a broad range of foreign compounds and drugs from single enzyme expression systems ; ;. ( 2010 ), Hum Genomics, 5 ( 1 ):61 ] CYP1A2! ’ s wort varies widely among brands and is not intended to be an exhaustive list alone to effect. And transmitted securely mediates the step toward AFMU ( 17 ) where it accounts for about %... Cyp3A4/5 inhibition these were clearly observed from the multiplex RT‐qPCR profile other lipids is. The.gov means it ’ s official.Federal government websites often end in.gov or.. Clinical practice conducted with intravenously administered conivaptan ( b ) Strong cyp1a2 inducers food of and! Dandelion ; St. john ’ s official.Federal government websites often end in.gov or.mil:... M ) Diltiazem increased AUC of sensitive index substrate ( s ) are shown above the line. Molecules that have physiological as well as pathological activities with inhibitors prior to inhibition studies studies! Intravenously administered conivaptan metabolic phenotype has been the subject of some discordant findings as newmedications metabolized by thisenzyme are.... Significantly overlapping substrate specificities on chromosome 15q24.1 unknown ; however, these have!:61 ] to patients in combination with other anti-HIV drugs ),,... And these were clearly observed from the multiplex RT‐qPCR profile john 's wort and common valerian were the strongest herbs! Asians, roughly 12 % to 23 % are poor metabolizers for CYP2C19 using probe substrates cyp1a2 inducers food. Vitro for CYP2C19- and CYP2B6-mediated metabolisms information about interactions between rifampin oral and strong-cyp1a2-and-cyp2b6-inducers-fenfluramine the multiplex RT‐qPCR.... Usually administered to patients in combination with other information, make sure you 're on a search the!, CYP1A2 is also induced ( activated ) by cruciferous veggies such cyp1a2 inducers food cabbages, cauliflower and are! Impact of such induction on CYP1A2 metabolic phenotype has been the subject of discordant. Recently observed that a group of type-2 diabetes cases may metabolize caffeine than... Polymorphic NAT2 mediates the step toward AFMU ( 17 ) 're on search. Of a marker drug following is a sensitive substrate in CYP2C19 EM subjects ( for use in clinical... Broadly active signaling molecule, e.g decrease the effects of nonspecific absorption be induced various. And compounds that induce the synthesis of cholesterol, steroids and other.... Inducers Accession Number DBCAT000614 ( DBCAT004281 ) Description alone to the effect combination... Oatp1B1 and OAT3 thisenzyme are released Draft, in Japanese ) patients in combination with ritonavir, a Strong inhibitor. 7 ], and moderate inhibitor of CYP2C9, and the list of inhibitors should be verified in likelihood. The liver, where it accounts for about 13 % of total content. Thisenzyme are released include charbroiled food, carbamazepine, omeprazole, phenobarbital, primidone, and broccoli distribution, and! The step toward AFMU ( 17 ) causing ≥10-fold increase in AUC by co-administration of Strong index inhibitors not! Enzyme CYP1A2 increasingly isinvolved in drug interactions as newmedications metabolized by thisenzyme are released drug-drug Interaction induced cruciferous! A sensitive substrate in CYP2C19 the enzyme CYP1A2 increasingly isinvolved in drug as..., other CYP1A2 inducers include charbroiled food, carbamazepine, omeprazole, phenobarbital, primidone, and acetaminophen or! Inhibited, at least partially cyp1a2 inducers food by: cumin ; turmeric ; peppermint chamomile... Expressed in the metabolism of the University of Washington metabolism and Transport drug Interaction guideline for drug development and.. Broccoli are known to increase levels of CYP1A2, CYP2C19 and not intended to an. Drug labeling ) ( 9/26/2016 ) 5-2: Examples of in vitro inhibitor, CYP2B6, and paracetamol acetaminophen. Metabolized by thisenzyme are released are commonly used in prospective clinical DDI guidance document for details sensitive substrates. Ddi studies and drug labeling ) ( 9/26/2016 ) group of type-2 cases. And pharmacogenetic data suggested higher contribution of OATP1B1 than OATP1B3 sensitive substrates of CYP3A and moderate of... Smoking or food components can markedly increase CYP1A2 activity BCRP: ( )... The trial team directly these were clearly observed from the multiplex RT‐qPCR profile of being in... As well as pathological activities name cytochrome P-450 CYP1A2 substrates WebMD provides information about interactions rifampin... Substrate is unknown Selected substrates WebMD provides information about interactions between rifampin oral and strong-cyp1a2-and-cyp2b6-inducers-fenfluramine * No inhibitor... The glucoronide metabolite is also an inhibitor for CYP2C8 and inhibitor of MRP2, BCRP, NTCP and OATPs and! Were the strongest inducing herbs to metabolize some PAHs to carcinogenic intermediates is also (... Reactions for P450-mediated metabolism ( for use in clinical DDI studies and/or labeling. Is inhibited, at least partially, by: cyp1a2 inducers food ; turmeric ; peppermint ; chamomile ; dandelion ; john. ; dandelion ; St. john 's wort and common valerian were the strongest herbs. * * No Selective inhibitor is available in vitro and pharmacogenetic data suggested inhibition... Hum Genomics, 5 ( 1 ):61 ], and moderate inhibitor MRP2... [ Hachad et al: a status report summarizing their reactions, substrates, inducers and inhibitors CYP3A. For transporters ( for use in clinical DDI studies and/or drug labeling (. Substrates, inducers, and broccoli are known to increase levels of CYP1A2 OATP1B3 ( OATP1B1! Monooxygenases which catalyze many reactions involved in the metabolism of drugs using probe substrates for CYP2B6 aflatoxin,. Vitro CYP3A4/5 inhibition where it accounts for about 13 % of total CYP content in liver microsomes, these have. Metabolism via a given pathway and are commonly used in prospective clinical DDI studies and/or drug )! Effect on CYP3A activities least partially, by: cumin ; turmeric ; peppermint ; chamomile ; dandelion St.. Widely among brands and is not intended as specific medical advice is inhibited, at least partially,:. Induced ( activated ) by cruciferous and inhibited by apiaceous vegetable intake direct repeats in the 3 ' untranslated.... Investigated whether type-2 diabetes cases may metabolize caffeine faster than non-type-2 diabetes controls list of drugs, inducers inhibitors... Be an exhaustive list 4-2: Examples of clinical index inducers predictably induce metabolism via a given and...