ArticleScientific reports2019
Concomitant febuxostat enhances methotrexate-induced hepatotoxicity by inhibiting breast cancer resistance protein.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 25 citations in OpenAlex.
- Contribution of Organic Anion Transporter 3 in Delayed Elimination of Methotrexate by Concomitant Administration of Febuxostat.Biopharmaceutics & drug disposition · 2025Article
- Deciphering gene mutations in the efficacy and toxicity of antineoplastic drugs: an oncology pharmacist's perspective.Frontiers in pharmacology · 2025Review
- Celebrating Versatility: Febuxostat's Multifaceted Therapeutic Application.Life (Basel, Switzerland) · 2023Review
- Methotrexate-related adverse events and impact of concomitant treatment with folic acid and tumor necrosis factor-alpha inhibitors: An assessment using the FDA adverse event reporting system.Frontiers in pharmacology · 2023Article
- Possibility of Multiple Drug-Drug Interactions in Patients Treated with Statins: Analysis of Data from the Japanese Adverse Drug Event Report (JADER) Database and Verification by Animal Experiments.International journal of medical sciences · 2022Article
- Ganciclovir and Its Hemocompatible More Lipophilic Derivative Can Enhance the Apoptotic Effects of Methotrexate by Inhibiting Breast Cancer Resistance Protein (BCRP).International journal of molecular sciences · 2021Article
- Hypouricemic agents reduce indoxyl sulfate excretion by inhibiting the renal transporters OAT1/3 and ABCG2.Scientific reports · 2021Article
- An Integrated In Silico and In Vivo Approach to Identify Protective Effects of Palonosetron in Cisplatin-Induced Nephrotoxicity.Pharmaceuticals (Basel, Switzerland) · 2020Article
- The advances of methotrexate resistance in rheumatoid arthritis.Inflammopharmacology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methotrexate (MTX) is an antifolate agent used for the treatment of various malignancies and is eliminated by breast cancer resistance protein (BCRP). Because febuxostat (FBX) is known to inhibit BCRP activity, FBX might exacerbate MTX-related adverse effects. In this study, we examined the drug-drug interaction between FBX and MTX in BCRP-expressing membrane vesicles. Moreover, we retrospectively investigated the impact of FBX on MTX-related adverse effects in 38 patients (144 cycles) receiving high-dose MTX therapy (HDMTX). The Food and Drug Administration Adverse Event Reporting System (FAERS) database and human hepatocellular carcinoma cell line HepG2 cells were used to evaluate the effects of FBX on MTX-induced hepatotoxicity. In the membrane vesicle study, FBX significantly inhibited BCRP-mediated transport of MTX. Concomitant FBX significantly increased the incidence of hepatotoxicity, but not of nephrotoxicity and hematological toxicity in patients receiving HDMTX. FAERS database analyses revealed that the reporting odds ratio of FBX for MTX-induced hepatotoxicity was 4.16 (95% CI: 2.89-5.98). Co-incubated FBX significantly decreased the cell viability and increased cytotoxicity in MTX-treated HepG2 cells. These findings suggest that concomitant FBX enhances MTX-induced hepatotoxicity by inhibiting hepatic BCRP. These findings provide important information for the safe management of HDMTX therapy in clinical settings.
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