{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:15:07Z","timestamp":1792199707962,"version":"4.4.0"},"reference-count":128,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Berberine, an isoquinoline alkaloid present in Berberis spp., Coptis chinensis and Hydrastis canadensis, is among the most widely consumed metabolic-health supplements, popularized as \u201cnature\u2019s Ozempic\u201d. Concurrent, often undisclosed use with prescription drugs is common in older adults, yet berberine is far from inert. Objective: To synthesize the evidence on berberine as a perpetrator of supplement\u2013drug interactions, propose a four-axis mechanistic taxonomy, with product quality treated separately as a modifier of exposure rather than as a mechanism, and derive a clinically actionable risk-stratification framework. Methods: Structured narrative review, prepared per the SANRA quality criteria; PubMed\/MEDLINE, Scopus, Web of Science and Embase were searched up to May 2026. Results: Despite very low systemic exposure (oral bioavailability 0.68% in rats; low ng\/mL plasma concentrations in humans), high luminal, enterocytic and hepatic concentrations generate interaction liability, documented in humans for a few pairs and mechanistic for most, along four mechanistic axes: inhibition, and transcriptional induction, of CYP3A4, with CYP2D6\/CYP2C9 inhibition that is quasi-irreversible through a metabolite-intermediate complex; transporter modulation (P-glycoprotein, OCT1\/OCT2, and MATE1); pharmacodynamic additivity (hypoglycemia, hypotension, and QT prolongation); and microbiome- and gut-barrier-mediated effects, the last of these being a candidate axis rather than a demonstrated one. Product-quality variability is treated separately, as a modifier of exposure. The clinical anchor is increased cyclosporine exposure in renal-transplant recipients (AUC +34.5%; trough 29.3% above control). These elements are integrated into a three-tier risk-stratification framework that combines perpetrator potency, victim-drug vulnerability, and patient vulnerability, with each tier being linked to a defined pharmacy action. Conclusions: In patients on multiple medications, and particularly when berberine is co-administered with drugs of narrow therapeutic index, it should be managed as an active pharmacological perpetrator rather than as an inert supplement. Unstandardized product quality and an unsettled European regulatory framework, under which national limits differ by more than an order of magnitude, further widen the uncertainty around the dose actually delivered. Berberine use should therefore be elicited routinely at medication reconciliation and stratified by mechanism, by victim-drug vulnerability, and by patient risk, with particular attention to metabolic self-medication in the GLP-1 era.<\/jats:p>","DOI":"10.3390\/ph19081313","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:48:31Z","timestamp":1787219311000},"page":"1313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification\u2014A Narrative Review"],"prefix":"10.3390","volume":"19","author":[{"given":"Caterina Nela","family":"Dumitru","sequence":"first","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 35 Al. I. Cuza Street, 800010 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodora","family":"Marcu","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 35 Al. I. Cuza Street, 800010 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5657-5456","authenticated-orcid":false,"given":"Alina Oana","family":"Dumitru","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 35 Al. I. Cuza Street, 800010 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona Steliana","family":"Tudor","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 35 Al. I. Cuza Street, 800010 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1514-953X","authenticated-orcid":false,"given":"Ionela Daniela","family":"Fer\u021bu","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 35 Al. I. Cuza Street, 800010 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina-Mihaela","family":"Elisei","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 35 Al. I. Cuza Street, 800010 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Goroftei","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 35 Al. I. Cuza Street, 800010 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jacc.2009.07.074","article-title":"Use of herbal products and potential interactions in patients with cardiovascular diseases","volume":"55","author":"Tachjian","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1055\/s-0031-1298331","article-title":"Pharmacokinetic herb-drug interactions (part 2): Drug interactions involving popular botanical dietary supplements and their clinical relevance","volume":"78","author":"Gurley","year":"2012","journal-title":"Planta Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e711","DOI":"10.3399\/bjgp18X699101","article-title":"Prevalence of drug-herb and drug-supplement interactions in older adults: A cross-sectional survey","volume":"68","author":"Agbabiaka","year":"2018","journal-title":"Br. J. Gen. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2165\/00002512-200926050-00006","article-title":"Prevalence of polypharmacy, polyherbacy, nutritional supplement use and potential product interactions among older adults living on the United States-Mexico border: A descriptive, questionnaire-based study","volume":"26","author":"Loya","year":"2009","journal-title":"Drugs Aging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s40266-017-0501-7","article-title":"Concurrent Use of Prescription Drugs and Herbal Medicinal Products in Older Adults: A Systematic Review","volume":"34","author":"Agbabiaka","year":"2017","journal-title":"Drugs Aging"},{"key":"ref_6","first-page":"e92363","article-title":"Pharmacological Interactions Between Nutritional Supplements and Prescription Medications in Older Adults: A Comprehensive Review","volume":"17","author":"Changaramkumarath","year":"2025","journal-title":"Cureus"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Djuv, A., Nilsen, O.G., and Steinsbekk, A. (2013). The co-use of conventional drugs and herbs among patients in Norwegian general practice: A cross-sectional study. BMC Complement. Altern. Med., 13.","DOI":"10.1186\/1472-6882-13-295"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1503\/cmaj.120951","article-title":"Grapefruit-medication interactions: Forbidden fruit or avoidable consequences?","volume":"185","author":"Bailey","year":"2013","journal-title":"CMAJ"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/0140-6736(91)90872-M","article-title":"Interaction of citrus juices with felodipine and nifedipine","volume":"337","author":"Bailey","year":"1991","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1093\/ajcn\/83.5.1097","article-title":"A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction","volume":"83","author":"Paine","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1016\/j.jfda.2018.01.009","article-title":"Food-drug interactions precipitated by fruit juices other than grapefruit juice: An update review","volume":"26","author":"Chen","year":"2018","journal-title":"J. Food Drug Anal."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Och, A., Och, M., Nowak, R., Podg\u00f3rska, D., and Podg\u00f3rski, R. (2022). Berberine, a Herbal Metabolite in the Metabolic Syndrome: The Risk Factors, Course, and Consequences of the Disease. Molecules, 27.","DOI":"10.3390\/molecules27041351"},{"key":"ref_13","unstructured":"Operation Supplement Safety (OPSS) (2026, June 27). Berberine: The Hype for \u201cNature\u2019s Ozempic\u201d, Consortium for Health and Military Performance, Available online: https:\/\/www.opss.org\/article\/berberine-hype-natures-ozempic."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/ptr.6252","article-title":"Berberine and barberry (Berberis vulgaris): A clinical review","volume":"33","author":"Imenshahidi","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Neag, M.A., Mocan, A., Echeverr\u00eda, J., Pop, R.M., Bocsan, C.I., Cri\u015fan, G., and Buzoianu, A.D. (2018). Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00557"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/13880209.2019.1577466","article-title":"Coptidis Rhizoma: A comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology","volume":"57","author":"Wang","year":"2019","journal-title":"Pharm. Biol."},{"key":"ref_17","first-page":"516","article-title":"Toxicology effects of Berberis vulgaris (barberry) and its active constituent, berberine: A review","volume":"20","author":"Rad","year":"2017","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1038\/nm1135","article-title":"Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins","volume":"10","author":"Kong","year":"2004","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-3-319-41334-1_2","article-title":"Berberine and Its Role in Chronic Disease","volume":"928","author":"Cicero","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.2337\/db06-0006","article-title":"Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states","volume":"55","author":"Lee","year":"2006","journal-title":"Diabetes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.nbt.2009.03.005","article-title":"AMP-activated protein kinase: A potential target for the diseases prevention by natural occurring polyphenols","volume":"26","author":"Hwang","year":"2009","journal-title":"New Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.metabol.2009.07.029","article-title":"Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression","volume":"59","author":"Zhang","year":"2010","journal-title":"Metabolism"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.atherosclerosis.2008.02.004","article-title":"Berberine decreases PCSK9 expression in HepG2 cells","volume":"201","author":"Cameron","year":"2008","journal-title":"Atherosclerosis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejphar.2016.11.055","article-title":"Non-coding RNAs and Berberine: A new mechanism of its anti-diabetic activities","volume":"795","author":"Chang","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"591654","DOI":"10.1155\/2012\/591654","article-title":"Berberine in the treatment of type 2 diabetes mellitus: A systemic review and meta-analysis","volume":"2012","author":"Dong","year":"2012","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jep.2014.09.049","article-title":"Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension","volume":"161","author":"Lan","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2074610","DOI":"10.1155\/2021\/2074610","article-title":"The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"2021","author":"Guo","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1517\/14712598.2012.704014","article-title":"Berberine on metabolic and cardiovascular risk factors: An analysis from preclinical evidences to clinical trials","volume":"12","author":"Derosa","year":"2012","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xie, W., Su, F., Wang, G., Peng, Z., Xu, Y., Zhang, Y., Xu, N., Hou, K., Hu, Z., and Chen, Y. (2022). Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1015045"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, J., Bi, C., Xi, H., and Wei, F. (2024). Effects of administering berberine alone or in combination on type 2 diabetes mellitus: A systematic review and meta-analysis. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1455534"},{"key":"ref_31","first-page":"167","article-title":"Preliminary study about the possible glycemic clinical advantage in using a fixed combination of Berberis aristata and Silybum marianum standardized extracts versus only Berberis aristata in patients with type 2 diabetes","volume":"5","author":"Putignano","year":"2013","journal-title":"Clin. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1080\/19390211.2017.1347227","article-title":"Variability in Potency Among Commercial Preparations of Berberine","volume":"15","author":"Funk","year":"2018","journal-title":"J. Diet. Suppl."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Singh, N., and Sharma, B. (2018). Toxicological Effects of Berberine and Sanguinarine. Front. Mol. Biosci., 5.","DOI":"10.3389\/fmolb.2018.00021"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ichim, M.C. (2019). The DNA-based authentication of commercial herbal products reveals their globally widespread adulteration. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01227"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00228-011-1108-2","article-title":"Repeated administration of berberine inhibits cytochromes P450 in humans","volume":"68","author":"Guo","year":"2012","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1055\/s-2007-981550","article-title":"An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents","volume":"73","author":"Etheridge","year":"2007","journal-title":"Planta Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/bdd.2112","article-title":"Renal vectorial transport of berberine mediated by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins 1 (MATE1) in rats","volume":"39","author":"Shi","year":"2018","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.metabol.2008.01.013","article-title":"Efficacy of berberine in patients with type 2 diabetes mellitus","volume":"57","author":"Yin","year":"2008","journal-title":"Metabolism"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1016\/S0735-1097(25)04048-3","article-title":"Berberine-induced torsades de pointes (TdP) [abstract]","volume":"85","author":"Rafique","year":"2025","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/j.1476-5381.1993.tb12836.x","article-title":"Electropharmacological effects of berberine on canine cardiac Purkinje fibres and ventricular muscle and atrial muscle of the rabbit","volume":"108","year":"1993","journal-title":"Br. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1208\/s12249-011-9632-z","article-title":"Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats","volume":"12","author":"Chen","year":"2011","journal-title":"AAPS PharmSciTech"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s00210-024-03326-x","article-title":"Effects of Berberis vulgaris, and its active constituent berberine on cytochrome P450: A review","volume":"398","author":"Bathaei","year":"2025","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"104722","DOI":"10.1016\/j.phrs.2020.104722","article-title":"Berberine pharmacology and the gut microbiota: A hidden therapeutic link","volume":"155","author":"Habtemariam","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1124\/dmd.115.066902","article-title":"Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements","volume":"44","author":"Sprouse","year":"2016","journal-title":"Drug Metab. Dispos."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100209","DOI":"10.1016\/j.obpill.2025.100209","article-title":"Dietary supplement considerations during glucagon-like Peptide-1 receptor agonist treatment: A narrative review","volume":"16","author":"Johnson","year":"2025","journal-title":"Obes. Pillars"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s40264-023-01392-3","article-title":"Drug-Drug Interactions Between Glucagon-Like Peptide 1 Receptor Agonists and Oral Medications: A Systematic Review","volume":"47","author":"Calvarysky","year":"2024","journal-title":"Drug Saf."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/phar.70007","article-title":"GLP-1RA-induced delays in gastrointestinal motility: Predicted effects on coadministered drug absorption by PBPK analysis","volume":"45","author":"Hooper","year":"2025","journal-title":"Pharmacotherapy"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1124\/dmd.110.033936","article-title":"Extensive intestinal first-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats","volume":"38","author":"Liu","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1021\/np400607k","article-title":"Berberine and its metabolites: Relationship between physicochemical properties and plasma levels after administration to human subjects","volume":"77","author":"Spinozzi","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.fitote.2016.02.001","article-title":"Research progress on berberine with a special focus on its oral bioavailability","volume":"109","author":"Liu","year":"2016","journal-title":"Fitoterapia"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ai, X., Yu, P., Peng, L., Luo, L., Liu, J., Li, S., Lai, X., Luan, F., and Meng, X. (2021). Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.762654"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1517\/13543784.2010.517745","article-title":"Berberine: A potential phytochemical with multispectrum therapeutic activities","volume":"19","author":"Vuddanda","year":"2010","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1208\/s12249-010-9520-y","article-title":"Physicochemical characterization of berberine chloride: A perspective in the development of a solution dosage form for oral delivery","volume":"11","author":"Battu","year":"2010","journal-title":"AAPS PharmSciTech"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1080\/17425255.2023.2203857","article-title":"Approaching strategy to increase the oral bioavailability of berberine, a quaternary ammonium isoquinoline alkaloid: Part 1. Physicochemical and pharmacokinetic properties","volume":"19","author":"Murakami","year":"2023","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1034\/j.1600-0773.2002.t01-1-910403.x","article-title":"The involvement of P-glycoprotein in berberine absorption","volume":"91","author":"Pan","year":"2002","journal-title":"Pharmacol. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9987097","DOI":"10.1155\/2021\/9987097","article-title":"Pharmacokinetics and Pharmacological Activities of Berberine in Diabetes Mellitus Treatment","volume":"2021","author":"Han","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tan, X.S., Ma, J.Y., Feng, R., Ma, C., Chen, W.J., Sun, Y.P., Fu, J., Huang, M., He, C.Y., and Shou, J.W. (2013). Tissue distribution of berberine and its metabolites after oral administration in rats. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077969"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1002\/jps.10268","article-title":"P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers","volume":"91","author":"Maeng","year":"2002","journal-title":"J. Pharm. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kim, H.G., Lee, H.S., Jeon, J.S., Choi, Y.J., Choi, Y.J., Yoo, S.Y., Kim, E.Y., Lee, K., Park, I., and Na, M. (2020). Quasi-Irreversible Inhibition of CYP2D6 by Berberine. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12100916"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"154288","DOI":"10.1016\/j.phymed.2022.154288","article-title":"Biodistribution and pharmacokinetic profile of berberine and its metabolites in hepatocytes","volume":"104","author":"Liu","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/1479-5876-9-62","article-title":"Bioactivities of berberine metabolites after transformation through CYP450 isoenzymes","volume":"9","author":"Li","year":"2011","journal-title":"J. Transl. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/s41596-018-0119-1","article-title":"INFOGEST static in vitro simulation of gastrointestinal food digestion","volume":"14","author":"Brodkorb","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s00228-021-03266-y","article-title":"Physiologically based pharmacokinetic model predictions of natural product-drug interactions between goldenseal, berberine, imatinib and bosutinib","volume":"78","author":"Adiwidjaja","year":"2022","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s40262-014-0188-4","article-title":"Predicting the effect of cytochrome P450 inhibitors on substrate drugs: Analysis of physiologically based pharmacokinetic modeling submissions to the US Food and Drug Administration","volume":"54","author":"Wagner","year":"2015","journal-title":"Clin. Pharmacokinet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ejps.2018.11.010","article-title":"Organic cation transporter and multidrug and toxin extrusion 1 co-mediated interaction between metformin and berberine","volume":"127","author":"Shi","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"12155","DOI":"10.1038\/srep12155","article-title":"Transforming berberine into its intestine-absorbable form by the gut microbiota","volume":"5","author":"Feng","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1016\/j.jfda.2018.01.013","article-title":"A regulatory science viewpoint on botanical-drug interactions","volume":"26","author":"Grimstein","year":"2018","journal-title":"J. Food Drug Anal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jep.2011.08.058","article-title":"Dose-response of berberine on hepatic cytochromes P450 mRNA expression and activities in mice","volume":"138","author":"Guo","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/ptr.3554","article-title":"The in vitro inhibition of human CYP1A2, CYP2D6 and CYP3A4 by tetrahydropalmatine, neferine and berberine","volume":"26","author":"Zhao","year":"2012","journal-title":"Phytother. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/cpt.3454","article-title":"Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans","volume":"117","author":"Morof","year":"2025","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1002\/mnfr.200600300","article-title":"Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: Effects of milk thistle, black cohosh, goldenseal, kava kava, St. John\u2019s wort, and Echinacea","volume":"52","author":"Gurley","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.clpt.2005.01.009","article-title":"In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4\/5 phenotypes","volume":"77","author":"Gurley","year":"2005","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/sj.clpt.6100222","article-title":"Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo","volume":"83","author":"Gurley","year":"2008","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1124\/dmd.31.11.1391","article-title":"Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components","volume":"31","author":"Chatterjee","year":"2003","journal-title":"Drug Metab. Dispos."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Xiao, G.M., Lu, T., Zhu, D., and Liu, M.Y. (2025). Berberine and berberrubine promote the expression of CYP3A4 via enhancing the binding of nuclear receptor PXR. BMC Pharmacol. Toxicol., 26.","DOI":"10.1186\/s40360-025-01026-7"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"International Transporter Consortium, Giacomini, K.M., Huang, S.M., Tweedie, D.J., Benet, L.Z., Brouwer, K.L., Chu, X., Dahlin, A., Evers, R., and Fischer, V. (2010). Membrane transporters in drug development. Nat. Rev. Drug Discov., 9, 215\u2013236.","DOI":"10.1038\/nrd3028"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/sj.bjc.6690710","article-title":"Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel","volume":"81","author":"Lin","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"673132","DOI":"10.1155\/2012\/673132","article-title":"Effects of berberine and hwangryunhaedok-tang on oral bioavailability and pharmacokinetics of ciprofloxacin in rats","volume":"2012","author":"Hwang","year":"2012","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Guo, L., Huang, J., Sun, Y., He, F., Zloh, M., and Wang, L. (2019). Inhibitory Effect of Berberine on Broiler P-glycoprotein Expression and Function: In Situ and In Vitro Studies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081966"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1002\/ptr.2808","article-title":"Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp","volume":"23","author":"Qiu","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e70126","DOI":"10.1002\/prp2.70126","article-title":"The Effects of Different Administration Regimens of Berberine Hydrochloride on the Pharmacokinetics of Sirolimus in Rats","volume":"13","author":"Yang","year":"2025","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s12272-014-0510-6","article-title":"Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin","volume":"38","author":"Kwon","year":"2015","journal-title":"Arch. Pharm. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1002\/cpt.2107","article-title":"Assessing Transporter-Mediated Natural Product\u2013Drug Interactions via In Vitro\u2013In Vivo Extrapolation: Clinical Evaluation with a Probe Cocktail","volume":"109","author":"Nguyen","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_84","first-page":"125","article-title":"Inhibitory effects of berberine on IK1, IK, and HERG channels of cardiac myocytes","volume":"22","author":"Li","year":"2001","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1159\/000363034","article-title":"Berberine induces hERG channel deficiency through trafficking inhibition","volume":"34","author":"Zhang","year":"2014","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/01.fjc.0000191564.52242.00","article-title":"Block of HERG channels by berberine: Mechanisms of voltage- and state-dependence probed with site-directed mutant channels","volume":"47","author":"Lara","year":"2006","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1527-3466.2001.tb00068.x","article-title":"Cardiovascular actions of berberine","volume":"19","author":"Lau","year":"2001","journal-title":"Cardiovasc. Drug Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/clc.4960110411","article-title":"Cardiovascular effects of berberine in patients with severe congestive heart failure","volume":"11","author":"Maciel","year":"1988","journal-title":"Clin. Cardiol."},{"key":"ref_89","first-page":"117","article-title":"Mechanistic effects and complications of berberine on cardiac arrhythmias: A systematic review","volume":"21","author":"Masoumi","year":"2026","journal-title":"Curr. Rev. Clin. Exp. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.hrcr.2022.03.018","article-title":"Harmless herbs? A case report of acquired long QT syndrome and torsades de pointes in a patient taking herbal supplements","volume":"8","author":"Burri","year":"2022","journal-title":"HeartRhythm  Case Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1177\/1715163516641136","article-title":"Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management","volume":"149","author":"Tisdale","year":"2016","journal-title":"Can. Pharm. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ejps.2015.05.009","article-title":"The enhancement of cardiac toxicity by concomitant administration of berberine and macrolides","volume":"76","author":"Zhi","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1056\/NEJMra032426","article-title":"Drug-induced prolongation of the QT interval","volume":"350","author":"Roden","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Spanakis, M., Bakaros, E., Papadopoulou, S.-N., Fournaraki, A., and Symvoulakis, E.K. (2025). Pharmacoepidemiological data on drug\u2013herb interactions: Serotonin syndrome, arrhythmias and the emerging role of artificial intelligence. Pharmacoepidemiology, 4.","DOI":"10.3390\/pharma4040022"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Wang, H., Zhang, H., Gao, Z., Zhang, Q., and Gu, C. (2022). The mechanism of berberine alleviating metabolic disorder based on gut microbiome. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.854885"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Yang, S., Li, D., Yu, Z., Li, Y., and Wu, M. (2021). Multi-Pharmacology of Berberine in Atherosclerosis and Metabolic Diseases: Potential Contribution of Gut Microbiota. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.709629"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Dehau, T., Cherlet, M., Croubels, S., Van De Vliet, M., Goossens, E., and Van Immerseel, F. (2023). Berberine-microbiota interplay: Orchestrating gut health through modulation of the gut microbiota and metabolic transformation into bioactive metabolites. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1281090"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1124\/mol.116.106617","article-title":"Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway","volume":"91","author":"Sun","year":"2017","journal-title":"Mol. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.7150\/thno.18290","article-title":"Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine","volume":"7","author":"Wang","year":"2017","journal-title":"Theranostics"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhao, Y., Zhang, M., Pang, X., Xu, J., Kang, C., Li, M., Zhang, C., Zhang, Z., and Zhang, Y. (2012). Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042529"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"14405","DOI":"10.1038\/srep14405","article-title":"Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats","volume":"5","author":"Zhang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.1038\/s41467-020-18414-8","article-title":"Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/s41586-019-1291-3","article-title":"Mapping human microbiome drug metabolism by gut bacteria and their genes","volume":"570","author":"Zimmermann","year":"2019","journal-title":"Nature"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nrmicro.2016.17","article-title":"The microbial pharmacists within us: A metagenomic view of xenobiotic metabolism","volume":"14","author":"Spanogiannopoulos","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1124\/pr.118.015768","article-title":"Gut reactions: Breaking down xenobiotic\u2013microbiome interactions","volume":"71","author":"Clarke","year":"2019","journal-title":"Pharmacol. Rev."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Dumitru, C.N., Dumitru, A.O., Goroftei, L., Nicule\u021b, E., Ignat, M.D., Baroiu, L., Nechita, A., and Balan, G. (2026). Pharmacomicrobiomics of non-antibiotic drugs: Mechanisms and clinical consequences of gut microbiota alterations. Pharmaceutics, 18.","DOI":"10.3390\/pharmaceutics18060651"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Dumitru, C.N., Mariana, L., Budacu, C.C., Mitea, G., Radu, M.D., Dumitru, A.O., Lupoae, A., Tatu, A., and Topor, G. (2025). Balancing the oral redox state: Endogenous and exogenous sources of reactive oxygen species and the antioxidant role of Lamiaceae and Asteraceae. Dent. J., 13.","DOI":"10.3390\/dj13050222"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Dumitru, C.N., Dumitru, A.O., Popa, G.V., Marcu, T., Ursu, M., Nechita, A., and Matei, N.M. (2026). The oral\u2013gut\u2013brain axis: From periodontal dysbiosis to neuroinflammation\u2014Mechanistic pathways, salivary and intestinal biomarkers, and therapeutic targets: A narrative review. Dent. J., 14.","DOI":"10.3390\/dj14050289"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Kwon, M., Lim, D.Y., Lee, C.H., Jeon, J.H., Choi, M.K., and Song, I.S. (2020). Enhanced Intestinal Absorption and Pharmacokinetic Modulation of Berberine and Its Metabolites through the Inhibition of P-Glycoprotein and Intestinal Metabolism in Rats Using a Berberine Mixed Micelle Formulation. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12090882"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Solnier, J., Zhang, Y., Kuo, Y.C., Du, M., Roh, K., Gahler, R., Wood, S., and Chang, C. (2023). Characterization and Pharmacokinetic Assessment of a New Berberine Formulation with Enhanced Absorption In Vitro and in Human Volunteers. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15112567"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.fct.2010.01.033","article-title":"Acute toxicity of berberine and its correlation with the blood concentration in mice","volume":"48","author":"Kheir","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1756284820961299","DOI":"10.1177\/1756284820961299","article-title":"Berberine for diarrhea in children and adults: A systematic review and meta-analysis","volume":"13","author":"Yu","year":"2020","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_113","unstructured":"European Union (2002). Directive 2002\/46\/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements. Off. J. Eur. Union, L 183, 51\u201357. Available online: https:\/\/eur-lex.europa.eu\/eli\/dir\/2002\/46\/oj."},{"key":"#cr-split#-ref_114.1","unstructured":"European Union (2006). Regulation"},{"key":"#cr-split#-ref_114.2","unstructured":"(EC) No 1925\/2006 of the European Parliament and of the Council of 20 December 2006 on the addition of vitamins and minerals and of certain other substances to foods. Off. J. Eur. Union, L 404, 26-38. Available online: https:\/\/eur-lex.europa.eu\/eli\/reg\/2006\/1925\/oj."},{"key":"ref_115","unstructured":"ANSES (French Agency for Food, Environmental and Occupational Health & Safety). (2026, August 08). Opinion on the Safety of Use of Berberine-Containing Plants in the Composition of Food Supplements, Available online: https:\/\/www.anses.fr\/en\/content\/use-berberine-containing-plants-food-supplements."},{"key":"ref_116","unstructured":"EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) (2026). Draft Scientific Opinion on the Safety of Plant Preparations Containing Berberine Pursuant to Article 8(2) of Regulation (EC) No 1925\/2006, EFSA. Available online: https:\/\/connect.efsa.europa.eu\/RM\/s\/consultations\/publicconsultation2\/a0lTk000007dHhh\/pc1841."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1358\/mf.2006.28.1.962774","article-title":"The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers","volume":"28","author":"Xin","year":"2006","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s00228-005-0952-3","article-title":"Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: Clinical and pharmacokinetic study","volume":"61","author":"Wu","year":"2005","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/clpt.2012.39","article-title":"The need for translational research on drug-drug interactions","volume":"91","author":"Hennessy","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1210\/clinem\/dgae719","article-title":"Clinical Consequences of Delayed Gastric Emptying With GLP-1 Receptor Agonists and Tirzepatide","volume":"110","author":"Jalleh","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e70070","DOI":"10.1111\/cob.70070","article-title":"Micronutrient and Nutritional Deficiencies Associated With GLP-1 Receptor Agonist Therapy: A Narrative Review","volume":"16","author":"Urbina","year":"2026","journal-title":"Clin. Obes."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"107587","DOI":"10.1016\/j.cdnut.2025.107587","article-title":"GLP-1 receptor agonists\u2014Good for body weight, bad for micronutrient status?","volume":"9","author":"Kerlikowsky","year":"2025","journal-title":"Curr. Dev. Nutr."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41366-025-01952-w","article-title":"Bridging the nutrition guidance gap for GLP-1 receptor agonist therapy assisted weight loss: Lessons from bariatric surgery","volume":"50","author":"Spreckley","year":"2026","journal-title":"Int. J. Obes."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41073-019-0064-8","article-title":"SANRA-a scale for the quality assessment of narrative review articles","volume":"4","author":"Baethge","year":"2019","journal-title":"Res. Integr. Peer Rev."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Munn, Z., Peters, M.D.J., Stern, C., Tufanaru, C., McArthur, A., and Aromataris, E. (2018). Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Med. Res. Methodol., 18.","DOI":"10.1186\/s12874-018-0611-x"},{"key":"ref_126","unstructured":"U.S. Food and Drug Administration (2026, July 27). Clinical Drug Interaction Studies\u2014Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions: Guidance for Industry, Available online: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/clinical-drug-interaction-studies-cytochrome-p450-enzyme-and-transporter-mediated-drug-interactions."},{"key":"ref_127","unstructured":"European Medicines Agency, Committee for Medicinal Products for Human Use (2026, June 27). Guideline on the Investigation of Drug Interactions (CPMP\/EWP\/560\/95\/Rev. 1), Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-investigation-drug-interactions-revision-1_en.pdf."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/8\/1313\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:58:13Z","timestamp":1787219893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/8\/1313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":128,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ph19081313"],"URL":"https:\/\/doi.org\/10.3390\/ph19081313","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}