(c) Also a substrate of MRP2. (b) Moderate inhibitor of CYP2C8 and weak inhibitor of CYP2B6. Table 3-1: Examples of clinical substrates for P450-mediated metabolism (for concomitant use clinical DDI studies and/or drug labeling) (12/03/2019). (f) Usually administered to patients in combination with ritonavir, a strong CYP3A inhibitor. (b) We currently do not have index inhibitors for CYP2B6. A higher dose (400 mg/day) modafinil had larger induction effect on CYP3A. 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. (o) Substrate of OCTs and MATEs. Cytochrome P450s CYP1A1 and CYP1A2 can metabolize a broad range of foreign compounds and drugs. (d) Strong inhibitor of CYP2C8 and inhibitor of OATP1B1 and OAT3. Drugs that may alter Gleevec plasma concentrations (Long List) 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. 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). (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. 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. 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). Drug Interaction Studies - Study Design, Data Analysis, and Implications for Dosing and Labeling. (b)In vitro and pharmacogenetic data suggested higher contribution of OATP1B1 than OATP1B3. (2010), Hum Genomics, 5(1):61)], and the list of references is available here. This information is generalized and not intended as specific medical advice. Vegetables such as cabbages, cauliflower and broccoli are known to increase levels of CYP1A2. 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. Table 5-1: Examples of clinical substrates for transporters (for use in clinical DDI studies and/or drug labeling) (12/03/2019). Table 1-2: Examples of in vitro selective inhibitors for P450-mediated metabolism (9/26/2016). Table 5-2: Examples of clinical inhibitors for transporters (for use in clinical DDI studies and drug labeling) (9/26/2016). (2010), Hum Genomics, 5(1):61], and the list of references is available here. (a) Listed based on an in vivo induction study and the observed effect might be partly attributable to induction of other pathway(s). (b) Strong inducer of CYP2C19, CYP3A, and moderate inducer of CYP1A2, CYP2B6, CYP2C8, CYP2C9. CYP2C9 inhibitors-amiodarone-Bactrim-fluconazole-fluoxetine-metronidazole-omeprazole. Here, we investigated whether type-2 diabetes cases may metabolize caffeine faster than non-type-2 diabetes controls. Table 1-3. 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. (b) OATP1B1 substrate. The impact of such induction on CYP1A2 metabolic phenotype has been the subject of some discordant findings. 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. (e) Sensitive substrate of CYP2D6 and moderate sensitive substrate of CYP3A. (a) We currently do not have sensitive index substrates for CYP2B6. Following is a table of selected substrates, inducers and inhibitors of CYP1A2. Sensitive substrates of CYP3A with ≥10-fold increase in AUC by co-administration of strong index inhibitors are shown above the dashed line. About 3% to 5% of Caucasians are poor metabolizers for CYP2C19?that is, they lack functioning genes for the synthesis of CYP2C19. Note: Index inhibitors predictably inhibit metabolism via a given pathway and are commonly used in prospective clinical DDI studies. 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. Appendectomy and cholecystectomy are acceptable. 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. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. (e) Also an inhibitor of MRP2. P-gp: (1) AUC fold-increase of digoxin ≥2 with co-administration and (2) in vitro inhibitor. Pirfenidone/Moderate CYP1A2 Inhibitors Interactions. 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. WHAT IS THE CYP1A2 GENE. WebMD provides information about interactions between Rifampin Oral and strong-cyp1a2-and-cyp2b6-inducers-fenfluramine. The .gov means it’s official.Federal government websites often end in .gov or .mil. Effect on CYP1A2 at lower doses of ritonavir is unknown. Note: (m) Diltiazem increased AUC of certain sensitive CYP3A substrates (e.g., buspirone) more than 5-fold. (i) Selective substrate of OATP1B1 (vs. OATP1B3). This table is prepared to provide examples of clinical index inducers and not intended to be an exhaustive list. of the main guidance documents for details. Specifically, it is involved in the metabolism of the xenobiotics caffeine, aflatoxin B1, and acetaminophen. Of CYP2C8 and inhibitor of CYP2C8 and inhibitor of CYP2C8 and inhibitor of CYP2C8 and inhibitor of CYP2C9 and.! H ) inhibitor of CYP2D6 University of Washington metabolism and Transport drug Interaction Database [ Hachad et.! 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