(c) Strong inhibitor of CYP2C8, weak inhibitor of CYP2B6, and inhibitor of OATP1B1. (i) Based on effect of 200 mg/day modafinil. (b) Strong inducer of CYP2C19, CYP3A, and moderate inducer of CYP1A2, CYP2B6, CYP2C8, CYP2C9. * Time-dependent inhibitors. 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]. (m) Diltiazem increased AUC of certain sensitive CYP3A substrates (e.g., buspirone) more than 5-fold. (b) Strong inducer of CYP3A and moderate inducer of CYP1A2, CYP2C19. 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. Home / Long List of Inhibitors and Inducers of CYP3A4 and CYP2D6. Table 5-1: Examples of clinical substrates for transporters (for use in clinical DDI studies and/or drug labeling) (12/03/2019). Note:(a) Also a substrate of OATP1B3. Note: Index inducers predictably induce metabolism via a given pathway and are commonly used in prospective clinical DDI studies. (2010), Hum Genomics, 5(1):61]. (c) Moderate sensitive substrates. 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 This table is prepared to provide examples of clinical index inducers and not intended to be an exhaustive list. OCT2/MATE: Well-established substrate of cationic transport system (metformin). i="">. (a)Most of P-gp inhibitors also inhibit CYP3A. Drug interaction guideline for drug development and labeling recommendations (Draft, in Japanese). CYP1A2 is encoded by the CYP1A2 gene located on chromosome 15q24.1. Most chemical inhibitors are not specific for an individual CYP enzyme. (c) Also an inhibitor of NTCP. Table 1-1: Examples of in vitro marker reactions for P450-mediated metabolism (9/26/2016). CYP1A2 is induced by cruciferous and inhibited by apiaceous vegetable intake. (e) Fexofenadine is a substrate for both P-gp and OATP1B. DrugFood interactions Caution w drugs that are inducers or inhibitors of CYP1A2 from NURSING 2361520162 at El Paso Community College See section IV.A.2. (a)In vitro data suggested higher contribution of OATP1B3 than OATP1B1. (g) Also an inhibitor of P-gp. (j) Ritonavir is usually given in combination with other anti-HIV or anti-HCV drugs in clinical practice. Other smaller feeding studies in humans have reported th… The CYP2D6 (20–30%), the CYP2C9 (10%), and the CYP2E1 and CYP1A2 (5%) complete this enzyme system. Pirfenidone/Moderate CYP1A2 Inhibitors Interactions. Appendectomy and cholecystectomy are acceptable. This table is prepared to provide examples of clinical index inducers and not intended to be an exhaustive list. Here, we investigated whether type-2 diabetes cases may metabolize caffeine faster than non-type-2 diabetes controls. Omeprazole and β‐naphthoflavone are known inducers for CYP1A2 which induce the transcription of CYP1A2 via AhR activation (Diaz et al. (b) Also a substrate of OATPs. September 2006. Table 1-3. 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. Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP1A2. Guidance for Industry. (a) Strong inducer of CYP1A2, CYP2C19, CYP3A, and moderate inducer of CYP2B6, CYP2C8, CYP2C9. (d) Weak inducer of CYP2B6, CYP2C9, and CYP2C19. Abbreviations: (c) Also a substrate of MRP2. 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). (o) Substrate of OCTs and MATEs. Drug Interaction Studies - Study Design, Data Analysis, and Implications for Dosing and Labeling. 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. [7], CYP1A2 also metabolizes polyunsaturated fatty acids into signaling molecules that have physiological as well as pathological activities. (b) We currently do not have index inhibitors for CYP2B6. CYP2C9 inducers … The polymorphic NAT2 mediates the step toward AFMU (17). Effect on CYP1A2 at lower doses of ritonavir is unknown. This table is prepared to provide examples of clinical inhibitors and is not intended to be an exhaustive list. (f) Moderate inducer of CYP2B6, CYP2C19 and CYP3A. This table is prepared to provide examples of clinical substrates and not intended to be an exhaustive list. 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. (b) OATP1B1 substrate. 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. 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. Addition of albumin to the study system should be considered to decrease the effects of nonspecific absorption. 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. Cytochrome P450s CYP1A1 and CYP1A2 can metabolize a broad range of foreign compounds and drugs. The inhibitors listed here can be used together with other information, such as metabolic profiles obtained from single enzyme expression systems. 1 CYP1A2 is exclusively expressed in the liver, where it accounts for about 13% of total CYP content in liver microsomes. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. (b)In vitro and pharmacogenetic data suggested higher contribution of OATP1B1 than OATP1B3. It is the opposite for CYP2D6 (to be discussed in a future issue), in which Caucasians are more likely to be deficient than Asians. 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. CYP2C9 substrates-warfarin-S-phenytoin-NSAIDs-ARBs-sulfonylureas. 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. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. Note:(a)Inhibitor of MRP2, BCRP, NTCP and OATPs. Table 3-3: Examples of clinical inducers for P450-mediated metabolisms (for concomitant use clinical DDI studies and/or drug labeling) (12/03/2019). (i) Also an inhibitor of OAT3. Table 4-2: Examples of in vitro inhibitors for transporters (9/26/2016). (2010), Hum Genomics, 5(1):61)], and the list of references is available here. (b) Also OATP1B1 substrate. 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. In Asians, roughly 12% to 23% are poor metabolizers for CYP2C19. In contrast, oral contraceptives, fluoroquinolones, and fluvoxamine inhibit CYP1A2 to a clinically relevant degree. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. (g) Strong inducer of CYP3A and moderate inducer of CYP2C9, and CYP2C19. 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. (c) Moderate inducer of CYP1A2 with dose of 800 mg/day ritonavir (not with other anti-HIV drugs). Before sharing sensitive information, make sure you're on a federal government site. 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