2003; Westerink and Schoonen 2007). (c)In vitro data suggested higher contribution of OAT1 than OAT3. (f) Also an inhibitor of OATPs. (c) Also an inhibitor of NTCP. (d) S-lansoprazole is a sensitive substrate in CYP2C19 EM subjects. AhR-mediated induction by smoking or food components can markedly increase CYP1A2 activity. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. Several urinary MRs have been proposed to assess CYP1A2 activity (4, 19â22). This table is prepared to provide examples of clinical inhibitors and is not intended to be an exhaustive list. (c) Also a substrate of MRP2. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. Before sharing sensitive information, make sure you're on a federal government site. Cytochrome P-450 1A2 (CYP1A2) is a biotransformation enzyme that activates several procarcinogens. 1 CYP1A2 is exclusively expressed in the liver, where it accounts for about 13% of total CYP content in liver microsomes. Caution should be used when extrapolating the observed effect of ritonavir alone to the effect of combination regimens on CYP3A activities. [15] Vegetables such as cabbages, cauliflower and broccoli are known to increase levels of CYP1A2. CYP1A2 is induced by cruciferous and inhibited by apiaceous vegetable intake. CYP1A2 is induced by cruciferous and inhibited by apiaceous vegetable intake. 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. (2010), Hum Genomics, 5(1):61)], and the list of references is available here. (a) Strong inducer of CYP1A2, CYP2C19, CYP3A, and moderate inducer of CYP2B6, CYP2C8, CYP2C9. 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]. i="">. Abbreviations: 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. (i) Based on effect of 200 mg/day modafinil. BCRP: (1) AUC fold-increase of sulfasalazine ≥1.5 with co-administration and (2) in vitro inhibitor. 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. Food Effect and CYP1A2 Induction Study in Healthy Subjects Please note that Smart Patients does not conduct clinical trials. The inhibitors listed here can be used together with other information, such as metabolic profiles obtained from single enzyme expression systems. CYP2C9 substrates-warfarin-S-phenytoin-NSAIDs-ARBs-sulfonylureas. [6], CYP1A2 is a member of the cytochrome P450 superfamily of enzymes. The polymorphic NAT2 mediates the step toward AFMU (17). However, these enzymes have significantly overlapping substrate specificities. September 2006. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. 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. It is reported that the estimated Ki value in inhibition studies tends to be lower. 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. (g) Strong inhibitors of CYP2C19 and CYP2D6. The evaluation of the final flu-voxamine PBPK model, including the fluvoxamine fraction 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). 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. OATP1B1). (e) Also an inhibitor of MRP2. Table 2-3: Examples of clinical index inducers for P450-mediated metabolisms (for use in index clinical DDI studies) (9/26/2016). OCT2/MATE: Well-established substrate of cationic transport system (metformin). Drug Metab Rev 1997;29:413-580. AUC: area under the concentration-time curve; CYP: cytochrome P450; DDI: drug-drug interaction; EM: extensive metabolizer; OATP1B1: organic anion transporting polypeptide 1B1. (h) The effect of St. John’s wort varies widely and is preparation-dependent. Table 4-2: Examples of in vitro inhibitors for transporters (9/26/2016). (m) Also a substrate of OATP1B1. (i) Selective substrate of OATP1B1 (vs. OATP1B3). (a) We currently do not have sensitive index substrates for CYP2B6. 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). of the main clinical DDI guidance document for details. (f) Also a substrate of NTCP. 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. 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). CYP1A2 is also induced (activated) by cruciferous veggies such as cabbage, cauliflower, and broccoli. (o) Substrate of OCTs and MATEs. (g) Selective substrate of OATP1B3 (vs. (b) Also a substrate of OATPs. 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.