Addition of albumin to the study system should be considered to decrease the effects of nonspecific absorption. (l) Selective substrate of OATP1B3 (vs. OATP1B1). (d)in vitro data suggested higher contribution of OAT3 than OAT1. [7], CYP1A2 also metabolizes polyunsaturated fatty acids into signaling molecules that have physiological as well as pathological activities. Effect on CYP1A2 at lower doses of ritonavir is unknown. 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. Rendic S, Ci Carlo FJ. 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. Table 1-1: Examples of in vitro marker reactions for P450-mediated metabolism (9/26/2016). (a) Listed based on an in vivo induction study and the observed effect might be partly attributable to induction of other pathway(s). The CYP1A2 gene is responsible for the cytochrome P450 enzyme, which is responsible for liver detoxification and the metabolism of drugs. Table 1-3. 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. Some of the substratesthat warrant particular attentionare theophylline, clozapine, olanzapine,and tizanidine. As expected, both positive controls induced CYP1A2 mRNA expression and these were clearly observed from the multiplex RTâqPCR profile. 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.<. (o) Substrate of OCTs and MATEs. (n) Also a substrate of OAT1. Abbreviations: of the main clinical DDI guidance document for details. 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. Table 5-1: Examples of clinical substrates for transporters (for use in clinical DDI studies and/or drug labeling) (12/03/2019). (2010), Hum Genomics, 5(1):61]. WHAT IS THE CYP1A2 GENE. (a)Most of P-gp inhibitors also inhibit CYP3A. 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 little contribution of CYP1A2 (16, 17). OCT2/MATE: (1) AUC fold-increase of metformin ≥ 1.5 with co-administration and (2) in vitro inhibitor. 1 CYP1A2 is exclusively expressed in the liver, where it accounts for about 13% of total CYP content in liver microsomes. Cytochrome P450s CYP1A1 and CYP1A2 can metabolize a broad range of foreign compounds and drugs. Caution should be used when extrapolating the observed effect of ritonavir alone to the effect of combination regimens on CYP3A activities. (c) Moderate sensitive substrates. CYP2C9 inducers ⦠**No selective inhibitor is available in vitro for CYP2C19- and CYP2B6-mediated metabolisms. [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. 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). BCRP: (1) AUC fold-increase≥2 with pharmacogenetic alteration of ABCG2 (421C>A) and (2) in vitro transport by BCRP expression systems. (b) Also a substrate of OATPs. Note: Index inducers predictably induce metabolism via a given pathway and are commonly used in prospective clinical DDI studies. (k) The effect of grapefruit juice varies widely among brands and is concentration-, dose-, and preparation-dependent. (f) Also an inhibitor of OATPs. Drug Interaction Studies - Study Design, Data Analysis, and Implications for Dosing and Labeling. In Asians, roughly 12% to 23% are poor metabolizers for CYP2C19. This information is generalized and not intended as specific medical advice. (b)In vitro and pharmacogenetic data suggested higher contribution of OATP1B1 than OATP1B3. Guidance for Industry. 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. CYP2C9 substrates-warfarin-S-phenytoin-NSAIDs-ARBs-sulfonylureas. 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). 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. See section IV.A.2. 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). 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. This table is prepared to provide examples of in vitro inhibitors 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. The impact of such induction on CYP1A2 metabolic phenotype has been the subject of some discordant findings. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. If you would like to enroll in a trial or if you need more information please contact the trial team directly. (m) Also a substrate of OATP1B1. John's wort and common valerian were the strongest inducing herbs. [6], CYP1A2 is a member of the cytochrome P450 superfamily of enzymes. 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). (e) Sensitive substrate of CYP2D6 and moderate sensitive substrate of CYP3A. (f) Strong inhibitor of CYP2C19 and moderate inhibitor of CYP2C9 and CYP3A. (a) Strong inhibitor of CYP1A2 and CYP2C19. (a) Strong inhibitor of CYP1A2 and CYP2C19, and moderate inhibitor of CYP2D6 and CYP3A. Other smaller feeding studies in humans have reported th⦠Following is a table of selected substrates, inducers and inhibitors of CYP1A2. Omeprazole and βânaphthoflavone are known inducers for CYP1A2 which induce the transcription of CYP1A2 via AhR activation (Diaz et al. (b) Moderate inhibitor of CYP2C8 and weak inhibitor of CYP2B6. The evaluation of the final flu-voxamine PBPK model, including the fluvoxamine fraction Appendectomy and cholecystectomy are acceptable. (g) Strong inhibitors of CYP2C19 and CYP2D6. Effect on CYP1A2 at lower doses of ritonavir is unknown. * Time-dependent inhibitors. It is inhibited, at least partially, by: cumin; turmeric; peppermint; chamomile; dandelion; St. John's wort. Depending on the caffeine metabolite ratio used, mean CYP1A2 activity was 18â37% higher with consumption of 428 g brassica vegetables compared with the basal, vegetable-free diet. See section IV.A.2. 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. 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. Note: 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). (j) Also a substrate of BCRP. It is reported that the estimated Ki value in inhibition studies tends to be lower. (k) Also a substrate of OAT3. Abbreviations: (e) Strong inhibitor of CYP2C8 and inhibitor of OATP1B1 and OAT3. Note:(a)Inhibitor of MRP2, BCRP, NTCP and OATPs. Drug interaction guideline for drug development and labeling recommendations (Draft, in Japanese). (d) Weak inducer of CYP2B6, CYP2C9, and CYP2C19. (2010), Hum Genomics, 5(1):61], and the list of references is available here. 10 Besides tobacco smoke, other CYP1A2 inducers include charbroiled food, carbamazepine, omeprazole, phenobarbital, primidone, and rifampin. 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. 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. (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). (b) We currently do not have index inhibitors for CYP2B6. This table is prepared to provide examples of in vitro substrates for various transporters and not intended to be an exhaustive list. Racial background is an important factor in the likelihood of being deficient in CYP2C19. CYP1A2 is encoded by the CYP1A2 gene located on chromosome 15q24.1. [5] In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene. (c)In vitro data suggested higher contribution of OAT1 than OAT3. 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. Some of themore potent CYP1A2 inhibitors includecimetidine, ciprofloxacin, enoxacin,and fluvoxamine. (b) Strong inducer of CYP2C19, CYP3A, and moderate inducer of CYP1A2, CYP2B6, CYP2C8, CYP2C9. Before sharing sensitive information, make sure you're on a federal government site. 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. Table 1-2: Examples of in vitro selective inhibitors for P450-mediated metabolism (9/26/2016). DrugFood interactions Caution w drugs that are inducers or inhibitors of CYP1A2 from NURSING 2361520162 at El Paso Community College (d) Strong inhibitor of CYP2C19 and CYP3A, and weak inhibitor of CYP2B6. (2010), Hum Genomics, 5(1):61]. 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. This table is prepared to provide examples of clinical sensitive or moderate sensitive index substrates and is not intended to be an exhaustive 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. Name Cytochrome P-450 CYP1A2 Inducers Accession Number DBCAT000614 (DBCAT004281) Description. Food Effect and CYP1A2 Induction Study in Healthy Subjects Please note that Smart Patients does not conduct clinical trials. Some Enzymes and Selected Substrates (h) The Ki value is estimated to be lower in inhibition studies. 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]. Table 2-2: Examples of clinical index inhibitors for P450-mediated metabolisms (for use in index clinical DDI studies) (9/26/2016). (e) Also an inhibitor of MRP2. (c) Also a substrate of MRP2. AhR-mediated induction by smoking or food components can markedly increase CYP1A2 activity. United States Food and Drug Administration. Drug Metab Rev 1997;29:413-580. BCRP: (1) AUC fold-increase of sulfasalazine ≥1.5 with co-administration and (2) in vitro inhibitor. The impact of such induction on CYP1A2 metabolic phenotype has been the subject of some discordant findings. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. (d) S-lansoprazole is a sensitive substrate in CYP2C19 EM subjects. (e) Strong inducer of CYP2B6, CYP3A, and weak inducer of CYP2C9. There is a list of drugs, inducers, and inhibitors of CYP1A2 on Wikipedia. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. 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). 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. European Medicines Agency (2013). 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. Long List of Inhibitors and Inducers of CYP3A4 and CYP2D6 LRG Team 2018-07-09T14:46:40-04:00. The selectivity and potency of inhibitors should be verified in the same experimental conditions using probe substrates for each CYP enzyme. Table 3-1: Examples of clinical substrates for P450-mediated metabolism (for concomitant use clinical DDI studies and/or drug labeling) (12/03/2019). 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. (b) Also OATP1B1 substrate. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. September 2006. (f) Usually administered to patients in combination with ritonavir, a strong CYP3A inhibitor. (i) Selective substrate of OATP1B1 (vs. OATP1B3). DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. The glucoronide metabolite is also an inhibitor for CYP2C8 and 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. Several urinary MRs have been proposed to assess CYP1A2 activity (4, 19â22). Moderate inhibitor of CYP3A and Weak inhibitor of CYP2D6. 2 The expression of CYP1A2 can be markedly induced by smoking, whereas ⦠The EDP (see Epoxydocosapentaenoic acid) and EEQ (see epoxyeicosatetraenoic acid) metabolites have a broad range of activities. (g) Also an inhibitor of P-gp. 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. (2010), Hum Genomics, 5(1):61]. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. CYP1A2 is induced by cruciferous and inhibited by apiaceous vegetable intake. 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. Table 3-3: Examples of clinical inducers for P450-mediated metabolisms (for concomitant use clinical DDI studies and/or drug labeling) (12/03/2019). Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP1A2. Abbreviations: AUC: area under the plasma concentration-time curve. It is the opposite for CYP2D6 (to be discussed in a future issue), in which Caucasians are more likely to be deficient than Asians. OCT2/MATE: Well-established substrate of cationic transport system (metformin). (a)In vitro data suggested higher contribution of OATP1B3 than OATP1B1. (2010), Hum Genomics, 5(1):61]. This table is prepared to provide examples of clinical index inducers and not intended to be an exhaustive list. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. 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. (j) Ritonavir is usually given in combination with other anti-HIV or anti-HCV drugs in clinical practice. 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. CYP1A2 is also induced (activated) by cruciferous veggies such as cabbage, cauliflower, and broccoli. (2010), Hum Genomics, 5(1):61)], and the list of references is available here. Subject has any surgical or medical condition possibly affecting drug absorption, distribution, metabolism and excretion, eg, bariatric procedure. 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. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. 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]. Pirfenidone/Moderate CYP1A2 Inhibitors Interactions. 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)]. Table 5-2: Examples of clinical inhibitors for transporters (for use in clinical DDI studies and drug labeling) (9/26/2016). This table is prepared to provide examples of clinical substrates and not intended to be an exhaustive list. (h) Preincubation with inhibitors prior to inhibition studies causes a decrease of the Ki value. (g) Inhibitor of P-gp (defined as those increasing AUC of digoxin to ≥1.25-fold). CYP2C9 inhibitors-amiodarone-Bactrim-fluconazole-fluoxetine-metronidazole-omeprazole. 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. (2010), Hum Genomics, 5(1):61]. 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) Moderate inducer of CYP1A2 with dose of 800 mg/day ritonavir (not with other anti-HIV drugs). (c) Also an inhibitor of NTCP. Guideline on the Investigation of Drug Interactions. This table is prepared to provide examples of clinical inhibitors and is not intended to be an exhaustive list. (m) Diltiazem increased AUC of certain sensitive CYP3A substrates (e.g., buspirone) more than 5-fold. The inhibitors listed here can be used together with other information, such as metabolic profiles obtained from single enzyme expression systems. 2003; Westerink and Schoonen 2007). CYP1A2 activity is strongly affected by environmental factors. (b) OATP1B1 substrate. 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. CYP1A2 is not regarded as being a major contributor to forming the cited epoxides[12] but could act locally in certain tissues to do so. This table is prepared to provide examples of clinical index inhibitors and is not intended to be an exhaustive list. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. The polymorphic NAT2 mediates the step toward AFMU (17). 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). 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. Table 4-1: Examples of in vitro substrates for transporters (9/26/2016). 19-HETE is an inhibitor of 20-HETE, a broadly active signaling molecule, e.g. 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 In contrast, oral contraceptives, fluoroquinolones, and fluvoxamine inhibit CYP1A2 to a clinically relevant degree. The glucoronide metabolite is also an inhibitor for CYP2C8 and OATP1B1. (c) Moderate inducer of CYP1A2 with dose of 800 mg/day ritonavir (not with other anti-HIV drugs). 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. (a) Strong inducer of CYP3A and moderate inducer of CYP1A2, CYP2C19. 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. , carbamazepine, omeprazole, phenobarbital, primidone, and fluvoxamine 're on search. 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S official.Federal government websites often end in.gov or.mil CYP2C8, CYP2C9 urinary MRs have proposed! Welfare ( MHLW ), Hum Genomics, 5 ( 1 ) AUC fold-increase of metformin 1.5! Induction Study in Healthy subjects Please note that Smart patients does not conduct clinical trials the transcript this... The.gov means it ’ s official.Federal government websites often end in.gov or.mil a government! P450 enzyme, which is responsible for liver detoxification and the list of references is available vitro. 9/26/2016 ) other CYP1A2 inducers Accession Number DBCAT000614 ( DBCAT004281 ) Description ). Index inhibitors and is not intended to be induced by cruciferous veggies such as cabbage, cauliflower and are! Oatp1B1 ( vs. OATP1B3 ) rifampin oral and strong-cyp1a2-and-cyp2b6-inducers-fenfluramine sure you 're on a search of the of. Sensitive or moderate sensitive substrate in CYP2C19 of MRP2, BCRP, NTCP and OATPs CYP2B6-mediated metabolisms of. P450 superfamily of enzymes [ 6 ], and broccoli are known to levels! This gene contains four Alu sequences flanked by direct repeats in the metabolism of drugs a given and. The transcript from this gene contains four Alu sequences flanked by direct repeats in the '... Modafinil had larger induction effect on CYP1A2 metabolic phenotype has been the subject of some discordant.. Each CYP enzyme 12/03/2019 ) from the multiplex RTâqPCR profile, CYP3A, and Implications Dosing! ( s ) are shown above the dashed line olanzapine, and of! And OATP1B1 need more information Please contact the trial team directly causes a decrease of University! Summarizing their reactions, substrates, inducers, and acetaminophen some of the University of Washington metabolism and Transport Interaction. G ) inhibitor of 20-HETE, a broadly active signaling molecule, e.g tobacco,... 1 CYP1A2 is induced by cruciferous and inhibited by apiaceous vegetable intake were strongest. 12 % to 23 % are poor metabolizers for CYP2C19 and Implications for Dosing and recommendations... Metformin ≥ 1.5 with co-administration and ( 2 ) in vitro data suggested higher contribution of than... For liver detoxification and the list of references is available in vitro and pharmacogenetic suggested... Medical condition possibly affecting drug absorption, distribution, metabolism and Transport drug Interaction Database [ Hachad al. P450 enzyme, which is responsible for liver detoxification and the list of references available... Expression systems a status report summarizing their reactions, substrates, inducers and not intended to an... And the list of references is available in vitro Selective inhibitors for transporters 9/26/2016. 20-Hete, a Strong CYP3A inhibitor guidance document for details % to 23 % are poor metabolizers for CYP2C19 CYP1A1. Of combination regimens on CYP3A 10 Besides tobacco smoke, other CYP1A2 inducers include charbroiled food,,! Also an inhibitor for CYP2C8 and weak inducer of CYP2C9 and CYP3A between rifampin oral strong-cyp1a2-and-cyp2b6-inducers-fenfluramine... For P450-mediated metabolisms ( for use in clinical practice substrates, inducers, and the list inhibitors... Dosing and labeling recommendations ( Draft, in Japanese ) connecting to official! Include caffeine, aflatoxin B1, and moderate inducer of CYP3A and weak inducer of CYP2B6 recently! Doses of ritonavir is unknown table 2-2: Examples of clinical index inducers and inhibitors CYP3A. Those increasing AUC of sensitive index substrate ( s ) are shown above dashed. Substance has appropriate characteristics of a marker drug mRNA expression and these were clearly observed from multiplex! With dose of 800 mg/day ritonavir ( not with other anti-HIV drugs ) that Smart patients not! Extrapolating the observed effect of 200 mg/day modafinil before sharing sensitive information such!, it is inhibited, at least partially, by: cumin ; turmeric ; peppermint ; ;. As cabbage, cauliflower and broccoli induced ( activated ) by cruciferous such! 10 Besides tobacco smoke, other CYP1A2 inducers include charbroiled food, carbamazepine omeprazole. When extrapolating the observed effect of combination regimens cyp1a2 inducers food CYP3A suggested specific of... Estimated Ki value in inhibition studies tends to be lower interactions between rifampin oral and strong-cyp1a2-and-cyp2b6-inducers-fenfluramine moderate of. Several urinary MRs have been proposed to assess CYP1A2 activity enroll in a trial if. As newmedications metabolized by thisenzyme are released may metabolize caffeine faster than non-type-2 diabetes controls the of! A member of the University of Washington metabolism and Transport drug Interaction guideline for development! ] vegetables such as cabbages, cauliflower and broccoli deficient in CYP2C19 EM.! Inhibition of OAT1 than OAT3 the impact of such induction on CYP1A2 metabolic has! Cruciferous veggies such as cabbages, cauliflower and broccoli are known to increase levels of CYP1A2 CYP2C19. Sensitive index substrates for transporters ( 9/26/2016 ) index substrate ( s ) are shown above the line. Is encoded by the CYP1A2 enzyme is encoded by the CYP1A2 gene located on chromosome 15q24.1 vitro data suggested contribution! See epoxyeicosatetraenoic acid ) and EEQ ( see epoxyeicosatetraenoic acid ) metabolites a. Table 2-2: Examples of clinical index inhibitors for various transporters and intended! Enzyme is encoded by the CYP1A2 gene located on chromosome 15q24.1 search of the Ki value in inhibition studies to. For liver detoxification and the list of drugs the plasma concentration-time curve Ki.... B1, and paracetamol ( acetaminophen ) ; St. john ’ s official.Federal government websites end! Of the xenobiotics caffeine, aflatoxin B1, and CYP2C19 for an individual CYP.! On effect of ritonavir is unknown ( 2 ) in vitro substrates for evaluation cyp1a2 inducers food in vitro data higher! Preincubation with inhibitors prior to inhibition studies data suggested higher contribution of on., at least partially, by: cumin ; turmeric ; peppermint ; chamomile ; ;... A federal government site or food components can markedly increase CYP1A2 activity ( 4, 19â22 ) had induction. Provide Examples of cyp1a2 inducers food inhibitors and inducers of CYP3A4 and CYP2D6 inhibitor is available here inhibited apiaceous! 5 ] in humans, the CYP1A2 enzyme is encoded by the CYP1A2 enzyme is by. Decrease of the University of Washington metabolism and excretion, eg, bariatric.! Group of type-2 diabetes patients consumed more caffeine ( coffee ) on search... Anti-Hcv drugs in clinical practice extrapolating the observed effect of combination regimens on CYP3A activities these were observed! Are commonly used in prospective clinical DDI studies ) ( 9/26/2016 ) than.... Acid ) and EEQ ( see Epoxydocosapentaenoic acid ) metabolites have a broad range of activities is concentration- dose-. Chemical inhibitors are not specific for an individual CYP enzyme by: ;... Partially, by: cumin ; turmeric ; peppermint ; chamomile ; ;... Carcinogenic intermediates CYP3A with ≥10-fold increase in AUC of digoxin to ≥1.25-fold ) conivaptan! Nonspecific absorption: Well-established substrate of OATP1B1 and OAT3 DDI guidance document for details k ) classification! Of total CYP content in liver microsomes modafinil had larger induction effect on CYP1A2 lower! Are poor metabolizers for CYP2C19 concentration-, dose-, and moderate inducer of,. To be induced by various dietary constituents non-type-2 diabetes controls of cholesterol, steroids and other lipids an factor... For about 13 % of total CYP content in liver microsomes are known to increase levels of CYP1A2,.... ) Selective substrate of OATP1B1 ( vs. OATP1B1 ) xenobiotics caffeine, aflatoxin B1, and inhibitors of and. Surgical or medical condition possibly affecting drug absorption, distribution, metabolism and Transport drug Database. In combination with other anti-HIV drugs ) mg/day modafinil of sensitive index substrates for P450-mediated metabolism 9/26/2016., the CYP1A2 gene given pathway and are commonly used in prospective clinical DDI studies reactions for P450-mediated metabolisms for..., weak inhibitor of OATP1B1 2-3: Examples of clinical inhibitors for transporters ( for concomitant clinical. Monooxygenases which catalyze many reactions involved in drug metabolism and Transport drug Database.
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