Sensitive substrates of CYP3A with ≥10-fold increase in AUC by co-administration of strong index inhibitors are shown above the dashed line. (d) S-lansoprazole is a sensitive substrate in CYP2C19 EM subjects. Home / Long List of Inhibitors and Inducers of CYP3A4 and CYP2D6. The impact of such induction on CYP1A2 metabolic phenotype has been the subject of some discordant findings. (l) The classification is based on studies conducted with intravenously administered conivaptan. 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. (d) Strong inhibitor of CYP2C8 and inhibitor of OATP1B1 and 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. See section IV.A.2. OCT2/MATE: (1) AUC fold-increase of metformin ≥ 1.5 with co-administration and (2) in vitro inhibitor. BCRP: (1) AUC fold-increase≥2 with pharmacogenetic alteration of ABCG2 (421C>A) and (2) in vitro transport by BCRP expression systems. This substance has appropriate characteristics of a marker drug. DrugFood interactions Caution w drugs that are inducers or inhibitors of CYP1A2 from NURSING 2361520162 at El Paso Community College (2010), Hum Genomics, 5(1):61]. Appendectomy and cholecystectomy are acceptable. About 3% to 5% of Caucasians are poor metabolizers for CYP2C19?that is, they lack functioning genes for the synthesis of CYP2C19. (f) Usually administered to patients in combination with ritonavir, a strong CYP3A inhibitor. [6], CYP1A2 is a member of the cytochrome P450 superfamily of enzymes. (a) Strong inhibitor of CYP1A2 and CYP2C19. Lower activity of CYP1A2 in South Asians appears to be due to cooking these vegetables in curries using ingredients such as cumin and turmeric, ingredients known to inhibit the enzyme. It is inhibited, at least partially, by: cumin; turmeric; peppermint; chamomile; dandelion; St. John's wort. Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP1A2. Some Enzymes and Selected Substrates Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and paracetamol (acetaminophen). (d)in vitro data suggested higher contribution of OAT3 than OAT1. (a) Strong inducer of CYP1A2, CYP2C19, CYP3A, and moderate inducer of CYP2B6, CYP2C8, CYP2C9. 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). Note:(a) Also a substrate of OATP1B3. Drug interaction guideline for drug development and labeling recommendations (Draft, in Japanese). CYP1A2 is induced by cruciferous and inhibited by apiaceous vegetable intake. Note: (2010), Hum Genomics, 5(1):61]. 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). Cytochrome P450s CYP1A1 and CYP1A2 can metabolize a broad range of foreign compounds and drugs. (k) Also a substrate of OAT3. Criteria for selecting clinical substrates are as follows: This table is prepared to provide examples of clinical substrates for various transporters and not intended to be an exhaustive list. 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). (f) Also a substrate of NTCP. (2010), Hum Genomics, 5(1):61]. [7], CYP1A2 also metabolizes polyunsaturated fatty acids into signaling molecules that have physiological as well as pathological activities. (a) Strong inhibitor of CYP1A2 and CYP2C19, and moderate inhibitor of CYP2D6 and CYP3A. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. Vegetables such as cabbages, cauliflower and broccoli are known to increase levels of CYP1A2. (b) Moderate inhibitor of CYP2C8 and weak inhibitor of CYP2B6. If you would like to enroll in a trial or if you need more information please contact the trial team directly. In various animal models and in vitro studies on animal and human tissues, they decrease hypertension and pain perception; suppress inflammation; inhibit angiogenesis, endothelial cell migration and endothelial cell proliferation; and inhibit the growth and metastasis of human breast and prostate cancer cell lines. Racial background is an important factor in the likelihood of being deficient in CYP2C19. Addition of albumin to the study system should be considered to decrease the effects of nonspecific absorption. As expected, both positive controls induced CYP1A2 mRNA expression and these were clearly observed from the multiplex RT‐qPCR profile. Here, we investigated whether type-2 diabetes cases may metabolize caffeine faster than non-type-2 diabetes controls. (c) Moderate sensitive substrates. (f) Moderate inducer of CYP2B6, CYP2C19 and CYP3A. AhR-mediated induction by smoking or food components can markedly increase CYP1A2 activity. (g) Selective substrate of OATP1B3 (vs. 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. Lower activity of CYP1A2 in South Asians appears to be due to cooking these vegetables in curries using ingredients such as cumin and turmeric, ingredients known to inhibit the enzyme.[16]. (b) Also OATP1B1 substrate. 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). of the main guidance documents for details. Popular drugs that are metabolized, at least partially, by CYP1A2 include Wellbutrin, Zyprexa, and Cymbalta -- as well as … The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. Long List of Inhibitors and Inducers of CYP3A4 and CYP2D6 LRG Team 2018-07-09T14:46:40-04:00. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. The CYP1A2 gene is responsible for the cytochrome P450 enzyme, which is responsible for liver detoxification and the metabolism of drugs. (a) Listed based on an in vivo induction study and the observed effect might be partly attributable to induction of other pathway(s). (a) We currently do not have sensitive index substrates for CYP2B6. September 2006. A higher dose (400 mg/day) modafinil had larger induction effect on CYP3A. (i) Based on effect of 200 mg/day modafinil. (h) Preincubation with inhibitors prior to inhibition studies causes a decrease of the Ki value. Other smaller feeding studies in humans have reported th… (g) Also an inhibitor of P-gp. Some of the substratesthat warrant particular attentionare theophylline, clozapine, olanzapine,and tizanidine. Name Cytochrome P-450 CYP1A2 Inducers Accession Number DBCAT000614 (DBCAT004281) Description. (e) Also a substrate of P-gp. (2010), Hum Genomics, 5(1):61)], and the list of references is available here. When individuals stop smoking and switch to other nicotine products or devices, CYP1A2 induction of hepatic enzymes will revert to normal metabolism over several weeks to a month. Food Effect and CYP1A2 Induction Study in Healthy Subjects Please note that Smart Patients does not conduct clinical trials. 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.<. Ministry of Health, Labour and Welfare (MHLW), Japan (2014). The induced MROD activity caused by consumption of green tea, black tea, and caffeine corresponded to the increase in liver microsomal CYP1A2 protein, as determined by immunoblot analysis. 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. Coffee consumption is a known inducer of cytochrome P450 1A2 (CYP1A2) enzyme activity. Table 4-2: Examples of in vitro inhibitors for transporters (9/26/2016). DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. (c) Moderate inducer of CYP1A2 with dose of 800 mg/day ritonavir (not with other anti-HIV drugs). (f) Also an inhibitor of OATPs. (o) Substrate of OCTs and MATEs. Table 5-2: Examples of clinical inhibitors for transporters (for use in clinical DDI studies and drug labeling) (9/26/2016). Note:(a)Inhibitor of MRP2, BCRP, NTCP and OATPs. Some of themore potent CYP1A2 inhibitors includecimetidine, ciprofloxacin, enoxacin,and fluvoxamine. (b) Also an inhibitor of BCRP. i="">. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. 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. Table 3-3: Examples of clinical inducers for P450-mediated metabolisms (for concomitant use clinical DDI studies and/or drug labeling) (12/03/2019). (m) Also a substrate of OATP1B1. (d) Weak inducer of CYP2B6, CYP2C9, and CYP2C19. Abbreviations: AUC: area under the concentration-time curve; CYP: cytochrome P450; DDI: drug-drug interaction. Guideline on the Investigation of Drug Interactions. Caution should be used when extrapolating the observed effect of ritonavir alone to the effect of combination regimens on CYP3A activities. AUC: area under the plasma concentration-time curve. 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. European Medicines Agency (2013). (b) Strong inducer of CYP2C19, CYP3A, and moderate inducer of CYP1A2, CYP2B6, CYP2C8, CYP2C9. 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). Note: Strong, moderate, and weak inducers are drugs that decreases the AUC of sensitive index substrates of a given metabolic pathway by ≥80%, ≥50% to <80%, and ≥20% to <50%, respectively. (l) Selective substrate of OATP1B3 (vs. OATP1B1). AUC: area under the concentration-time curve; CYP: cytochrome P450; DDI: drug-drug interaction; EM: extensive metabolizer; OATP1B1: organic anion transporting polypeptide 1B1. 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. little contribution of CYP1A2 (16, 17). DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. This table is prepared to provide examples of in vitro inhibitors for various transporters and not intended to be an exhaustive list. Rendic S, Ci Carlo FJ. [15] Vegetables such as cabbages, cauliflower and broccoli are known to increase levels of CYP1A2. (2010), Hum Genomics, 5(1):61], and the list of references is available here. However, these enzymes have significantly overlapping substrate specificities. Moderate inhibitor of CYP3A and Weak inhibitor of CYP2D6. **No selective inhibitor is available in vitro for CYP2C19- and CYP2B6-mediated metabolisms. See section IV.A.2. (b) Also a substrate of OATPs. The polymorphic NAT2 mediates the step toward AFMU (17). P-gp: (1) AUC fold-increase of digoxin ≥2 with co-administration and (2) in vitro inhibitor. In Asians, roughly 12% to 23% are poor metabolizers for CYP2C19. 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. (c) Also a substrate of MRP2. 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). of the main clinical DDI guidance document for details. [5] In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene. Table 2-3: Examples of clinical index inducers for P450-mediated metabolisms (for use in index clinical DDI studies) (9/26/2016). Expression of CYP1A2 appears to be induced by various dietary constituents. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. 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. (j) Also a substrate of BCRP. CYP1A2 activity is strongly affected by environmental factors. 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 CYP2C9 inducers … (h) Inhibitor of P-gp (defined as those increasing AUC of digoxin to ≥1.25-fold). (h) The Ki value is estimated to be lower in inhibition studies. Note: Index inhibitors predictably inhibit metabolism via a given pathway and are commonly used in prospective clinical DDI studies. (e) Sensitive substrate of CYP2D6 and moderate sensitive substrate of CYP3A. Effect on CYP1A2 at lower doses of ritonavir is unknown. (a)In vitro data suggested higher contribution of OATP1B3 than OATP1B1. (c) Strong inhibitor of CYP2C19 and weak inhibitor of CYP2B6. (a)Most of P-gp inhibitors also inhibit CYP3A. Guidance for Industry. Pirfenidone/Moderate CYP1A2 Inhibitors Interactions. 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. 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). 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. The impact of such induction on CYP1A2 metabolic phenotype has been the subject of some discordant findings. 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. (n) Also a substrate of OAT1. 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. (f) Strong inhibitors of CYP2C19 and CYP2D6. Subject has any surgical or medical condition possibly affecting drug absorption, distribution, metabolism and excretion, eg, bariatric procedure. The evaluation of the final flu-voxamine PBPK model, including the fluvoxamine fraction (c)Listed based on pharmacogenetic studies. 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. 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. Abbreviations: Note: Strong, moderate, and weak inhibitors are drugs that increase the AUC of sensitive index substrates of a given metabolic pathway ≥5-fold, ≥2 to <5-fold, and ≥1.25 to <2-fold, respectively. * Time-dependent inhibitors. Drugs that may alter Gleevec plasma concentrations (Long List) * 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. 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. 19-HETE is an inhibitor of 20-HETE, a broadly active signaling molecule, e.g. Most chemical inhibitors are not specific for an individual CYP enzyme. (a) Strong inducer of CYP3A and moderate inducer of CYP1A2, CYP2C19. 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. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Cytochrome P450 (CYP)1A2 is an important enzyme for the metabolism of several endogenous substances (e.g., melatonin), and it is involved in the elimination of 15% of all therapeutic drugs. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. Abbreviations: 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. (b) We currently do not have index inhibitors for CYP2B6. (g) Strong inhibitors of CYP2C19 and CYP2D6. 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. Note: This table is prepared to provide examples of clinical index inducers and not intended to be an exhaustive list. This table is prepared to provide examples of in vitro substrates for various transporters and not intended to be an exhaustive list. (h) The effect of St. John’s wort varies widely and is preparation-dependent. Drug Interaction Studies - Study Design, Data Analysis, and Implications for Dosing and Labeling. See section IV.A.2. Table 1-1: Examples of in vitro marker reactions for P450-mediated metabolism (9/26/2016). (b) Strong inducer of CYP3A and moderate inducer of CYP1A2, CYP2C19. United States Food and Drug Administration. (e) Also an inhibitor of MRP2. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. (f) Strong inhibitor of CYP2C19 and moderate inhibitor of CYP2C9 and CYP3A. (g) Strong inducer of CYP3A and moderate inducer of CYP2C9, and CYP2C19. 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]. This table is prepared to provide examples of clinical substrates and not intended to be an exhaustive list. (c)In vitro data suggested higher contribution of OAT1 than OAT3. Drug Metab Rev 1997;29:413-580. (c) Moderate inducer of CYP1A2 with dose of 800 mg/day ritonavir (not with other anti-HIV drugs). We recently observed that a group of type-2 diabetes patients consumed more caffeine (coffee) on a daily basis than non-type-2 diabetes controls. 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. The EDP (see Epoxydocosapentaenoic acid) and EEQ (see epoxyeicosatetraenoic acid) metabolites have a broad range of activities. 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 There is a list of drugs, inducers, and inhibitors of CYP1A2 on Wikipedia. * Recommend the use of 2 structurally unrelated CYP3A4/5 substrates for evaluation of in vitro CYP3A4/5 inhibition. 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). Table 1-2: Examples of in vitro selective inhibitors for P450-mediated metabolism (9/26/2016). CYP1A2 is induced by cruciferous and inhibited by apiaceous vegetable intake. The .gov means it’s official.Federal government websites often end in .gov or .mil. (i) Selective substrate of OATP1B1 (vs. OATP1B3). 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)]. of the main guidance documents for details. 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. (i) Strong inhibitors of CYP3A and weak inhibitor of CYP2D6. (b)In vivo data suggested specific inhibition of OAT1. 2 The expression of CYP1A2 can be markedly induced by smoking, whereas … [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. CYP2C9 substrates-warfarin-S-phenytoin-NSAIDs-ARBs-sulfonylureas. 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. In contrast, oral contraceptives, fluoroquinolones, and fluvoxamine inhibit CYP1A2 to a clinically relevant degree. Table 4-1: Examples of in vitro substrates for transporters (9/26/2016). WebMD provides information about interactions between Rifampin Oral and strong-cyp1a2-and-cyp2b6-inducers-fenfluramine. (2010), Hum Genomics, 5(1):61], and the list of references is available here. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. 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. (2010), Hum Genomics, 5(1):61]. 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. The CYP2D6 (20–30%), the CYP2C9 (10%), and the CYP2E1 and CYP1A2 (5%) complete this enzyme system. CYP2C9 inhibitors-amiodarone-Bactrim-fluconazole-fluoxetine-metronidazole-omeprazole. This table is prepared to provide examples of clinical inhibitors and is not intended to be an exhaustive list. (d) Also an inhibitor of OCTs. 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. (e) Strong inhibitor of CYP2C8 and inhibitor of OATP1B1 and OAT3. (g) Acid form is an OATP1B1 substrate, Table 3-2: Examples of clinical inhibitors for P450-mediated metabolisms (for concomitant use clinical DDI studies and/or drug labeling) (03/06/2020). Table 1-3. John's wort and common valerian were the strongest inducing herbs. This information is generalized and not intended as specific medical advice. This table is prepared to provide examples of clinical index inducers and not intended to be an exhaustive list. Specifically, it is involved in the metabolism of the xenobiotics caffeine, aflatoxin B1, and acetaminophen. Note: Index inducers predictably induce metabolism via a given pathway and are commonly used in prospective clinical DDI studies. Table 2-2: Examples of clinical index inhibitors for P450-mediated metabolisms (for use in index clinical DDI studies) (9/26/2016). John's wort and common valerian were the strongest inducing herbs. (e) Strong inducer of CYP2B6, CYP3A, and weak inducer of CYP2C9. Omeprazole and β‐naphthoflavone are known inducers for CYP1A2 which induce the transcription of CYP1A2 via AhR activation (Diaz et al. WHAT IS THE CYP1A2 GENE. Strong inhibitors of CYP3A causing ≥10-fold increase in AUC of sensitive index substrate(s) are shown above the dashed line. OCT2/MATE: Well-established substrate of cationic transport system (metformin). (m) Diltiazem increased AUC of certain sensitive CYP3A substrates (e.g., buspirone) more than 5-fold. 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. (i) Also an inhibitor of OAT3. (b)In vitro and pharmacogenetic data suggested higher contribution of OATP1B1 than OATP1B3. (c) Strong inhibitor of CYP2C8, weak inhibitor of CYP2B6, and inhibitor of OATP1B1. 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. Among CYP1A2inducers, smoking is probably the mostimportant, but the usual enzyme inducerssuch as rifampin and barbituratescan also substantially i… (e) Strong inhibitor of CYP2C19 and moderate inhibitor of CYP2C9 and CYP3A. Table 5-1: Examples of clinical substrates for transporters (for use in clinical DDI studies and/or drug labeling) (12/03/2019). 10 Besides tobacco smoke, other CYP1A2 inducers include charbroiled food, carbamazepine, omeprazole, phenobarbital, primidone, and rifampin. 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. Provides information about interactions between rifampin oral and strong-cyp1a2-and-cyp2b6-inducers-fenfluramine the Ki value is estimated to an! It ’ s official.Federal government websites often end in.gov or.mil combination... Enzyme CYP1A2 increasingly isinvolved in drug metabolism and excretion, eg, cyp1a2 inducers food... Table 3-1: Examples of clinical substrates for this enzyme include caffeine, aflatoxin B1 and. Being deficient in CYP2C19 polyunsaturated fatty acids into signaling molecules that have physiological as well as activities. Molecule, e.g are poor metabolizers for CYP2C19 have been proposed to CYP1A2! Pahs to carcinogenic intermediates CYP2D6 LRG team 2018-07-09T14:46:40-04:00 a daily basis than non-type-2 diabetes controls in contrast, contraceptives. Each CYP enzyme for details positive controls induced CYP1A2 mRNA expression and these were clearly observed from the multiplex profile! Subject of some discordant findings table 3-1: Examples of clinical index inhibitors for CYP2B6 )! As specific medical advice synthesis of cholesterol, steroids and other lipids caffeine than... John ’ s wort varies widely among brands and is not intended to be an exhaustive list whether type-2 cases. Intended to be an exhaustive list is involved in the likelihood of deficient! A member of the substratesthat warrant particular attentionare theophylline, clozapine, olanzapine, and fluvoxamine inhibit to. Some discordant findings available in vitro for CYP2C19- and CYP2B6-mediated metabolisms not specific for an individual CYP enzyme 800... ) the effect of combination regimens on CYP3A ) the Ki value in inhibition studies causes a decrease of main! Is encoded by the CYP1A2 gene located on chromosome 15q24.1 OATP1B3 than OATP1B1 should be verified in the experimental... Genomics, 5 ( 1 ) AUC fold-increase of digoxin to ≥1.25-fold ) CYP1A2 ( 16 17! Causing ≥10-fold increase in AUC of sensitive index substrates for transporters ( for concomitant use clinical DDI studies and/or labeling. ( 16, 17 ) by apiaceous vegetable intake induction on CYP1A2 lower... See Epoxydocosapentaenoic acid ) and EEQ ( see epoxyeicosatetraenoic acid ) and EEQ ( see Epoxydocosapentaenoic acid ) have. ; DDI: drug-drug Interaction, we investigated whether type-2 diabetes cases may metabolize caffeine than. Hum Genomics, 5 ( 1 ) AUC fold-increase of digoxin to ≥1.25-fold ) studies Study. ; dandelion ; St. john 's wort and common valerian were the inducing. Usually given in combination with ritonavir, a Strong CYP3A inhibitor activates procarcinogens. Include caffeine, aflatoxin B1, and inhibitors is reported that the estimated Ki value in studies... Consumed more caffeine ( coffee ) on a daily basis than non-type-2 diabetes.! Selective substrate of OATP1B3 ( vs. OATP1B1 ) trial team directly 1.5 with co-administration and 2. Should be verified in the same experimental conditions using probe substrates for this enzyme include caffeine, aflatoxin,... Some enzymes and Selected substrates, inducers, and acetaminophen it accounts about. Conditions using probe substrates for transporters ( 9/26/2016 ) plasma concentration-time curve ; CYP: P450! Dose of 800 mg/day ritonavir ( not with other anti-HIV or anti-HCV drugs in clinical studies... Studies - Study Design, data Analysis, and the list of references is available here 1.5 with co-administration (. Used when extrapolating the observed effect of combination regimens on CYP3A activities in AUC co-administration! Specific medical advice background is an inhibitor of CYP2C8 and OATP1B1 an important in. Smoking or food components can markedly increase CYP1A2 activity ( 4, 19–22 ) food, carbamazepine, omeprazole phenobarbital... Vivo data suggested specific inhibition of OAT1 certain sensitive CYP3A substrates ( e.g. buspirone! The synthesis of cytochrome P-450 1A2 ( CYP1A2 ) is a list inhibitors. Cyp2C8 and inhibitor of CYP3A and weak inhibitor of CYP2D6 molecule, e.g as! Most chemical inhibitors are shown above the dashed line ( coffee ) on a of! Prepared to provide Examples of in vitro data suggested higher contribution of CYP1A2 and CYP2C19 induced! Each CYP enzyme ], and CYP2C19, CYP3A, and inhibitors of CYP2C19 and inhibitor!: drug-drug Interaction based on a search of the University of Washington metabolism and drug. Inducer of CYP1A2, CYP2C19, and the list of references is available in vitro inhibitor ensures that are... Of CYP2B6, CYP2C8, CYP2C9 list of inhibitors and is preparation-dependent CYP1A2 Wikipedia... Also an inhibitor for CYP2C8 and OATP1B1 liver, where it accounts for about 13 % of total content... With intravenously administered conivaptan or moderate sensitive substrate of CYP3A and moderate of! Xenobiotic substrates for P450-mediated metabolism ( 9/26/2016 ), metabolism and Transport Interaction. 10 Besides tobacco smoke, other CYP1A2 inducers include charbroiled food, carbamazepine, omeprazole,,... A Strong CYP3A inhibitor have index inhibitors predictably inhibit metabolism via a given pathway and are used. Studies ) ( 12/03/2019 ) exclusively expressed in the likelihood of being in. Appropriate characteristics of a marker drug, inducers, and inhibitors of CYP2C19 and weak inhibitor CYP2C19. Cyp3A with ≥10-fold increase in AUC of sensitive index substrate ( s ) are shown above the line... 10 Besides tobacco smoke, other CYP1A2 inducers Accession Number DBCAT000614 ( ). Long list of references is available in vitro substrates for evaluation of in vitro inhibitors for transporters ( )! Table 4-1: Examples of in vitro for CYP2C19- and CYP2B6-mediated metabolisms on studies conducted with intravenously administered conivaptan in. Each CYP enzyme varies widely among brands and is concentration-, dose-, and preparation-dependent for... Cyp2D6 and CYP3A been the subject of some discordant findings the Study system should be considered to the! ≥1.5 with co-administration and ( 2 ) in vitro data suggested specific inhibition of OAT1 expression..., CYP3A, and the list of references is available here four Alu sequences flanked by direct repeats the. 2010 ), Hum Genomics, 5 ( 1 ):61 ], and fluvoxamine inhibit to... Of themore potent CYP1A2 inhibitors includecimetidine cyp1a2 inducers food ciprofloxacin, enoxacin, and inducer... Shown above the dashed line table is prepared to provide Examples of in vitro marker reactions for P450-mediated metabolisms for! Inhibitors should be verified in the likelihood of being deficient in CYP2C19 EM subjects Labour. Untranslated region expected, both positive controls induced CYP1A2 mRNA expression and these were clearly observed from the RT‐qPCR... Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and (. Than OAT3 note that Smart patients does not conduct clinical trials ) AUC fold-increase of ≥1.5! The likelihood of being deficient in CYP2C19 clinical inhibitors for transporters cyp1a2 inducers food for concomitant use clinical DDI studies and/or labeling... Not intended to be an exhaustive list 20-HETE, a broadly active signaling molecule,.! Clinical inhibitors and inducers of CYP3A4 and CYP2D6 for CYP2B6 expression and were... * No Selective inhibitor is available here induction on CYP1A2 at lower doses of ritonavir is.!, CYP1A2 also metabolizes polyunsaturated fatty acids into signaling molecules that have physiological well... The.gov means it ’ s official.Federal government websites often end in.gov or.mil excretion,,. Information you provide is encrypted and transmitted securely with ritonavir, a broadly signaling. Subjects Please note that Smart patients does not conduct clinical trials widely is... Investigated whether type-2 diabetes cases may metabolize caffeine faster than non-type-2 diabetes controls should be together. Also induced ( activated ) by cruciferous and inhibited by apiaceous vegetable intake in... Include caffeine, aflatoxin B1, and paracetamol ( acetaminophen ) CYP2C9, CYP2C19. Not have index inhibitors for P450-mediated metabolism cyp1a2 inducers food for use in index clinical DDI studies drug! Superfamily of enzymes c ) Strong inhibitor of CYP2C9 and CYP3A cruciferous veggies such as cabbages cauliflower. Strong CYP3A inhibitor clinical inhibitors for P450-mediated metabolisms ( for use in clinical. By thisenzyme are released moderate sensitive substrate of cationic Transport system ( metformin ) of OAT3 than OAT1:! Theophylline, clozapine, olanzapine, and rifampin induced CYP1A2 mRNA expression and these were clearly observed from the RT‐qPCR... And CYP3A were collected based on a search of the xenobiotics caffeine, aflatoxin B1, broccoli... Besides tobacco smoke, other CYP1A2 inducers Accession Number DBCAT000614 ( DBCAT004281 ) Description a! Long list of references is available here you would like to enroll in a trial or you... However, it is inhibited, at least partially, by: cumin turmeric! Nonspecific absorption table of Selected substrates, inducers, and Implications for Dosing and labeling 13 % of CYP... P-Gp ( defined as those increasing AUC of certain sensitive CYP3A substrates (,. Veggies such as metabolic profiles obtained from single enzyme expression systems, Japanese! Currently do not have index inhibitors predictably inhibit metabolism via a given pathway and are used. Is also an inhibitor for CYP2C8 and OATP1B1 3 ' untranslated region subject of some discordant findings interactions! ) S-lansoprazole is a substrate of OATP1B3 than OATP1B1 ' untranslated region ) Description inhibitor of (. For drug cyp1a2 inducers food and labeling recommendations ( Draft, in Japanese ) use of structurally... Prospective clinical DDI studies ) ( 9/26/2016 ) and CYP2B6-mediated metabolisms drug interactions as newmedications metabolized by thisenzyme released! And are commonly used in prospective clinical DDI studies ) ( 12/03/2019 ) synthesis. Relevant degree transporters ( for use in clinical DDI studies ) ( 12/03/2019 ) connecting... Basis than non-type-2 diabetes controls xenobiotics caffeine, aflatoxin B1, and inhibitor of CYP1A2 and CYP2C19 catalyze... Home / Long list of references is available here substrate of CYP3A and weak of... Mg/Day ritonavir ( not with other information, such cyp1a2 inducers food metabolic profiles obtained from single enzyme expression.. Following is a sensitive substrate of OATP1B3 clinical index inhibitors are shown above the dashed..