ArticleCancer medicine2025
Impact of Methotrexate and 7-Hydroxymethotrexate Exposure on Renal Toxicity in Pediatric Non-Hodgkin Lymphoma.
Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Piribedil attenuates methotrexate-induced nephrotoxicity in rats: associated changes in miR-205/EGLN2, Nrf2, and PERK/ATF4/CHOP-related stress responses.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Role of CXCL16/ADAM10 signaling in methotrexate-induced nephrotoxicity and its modulation by simvastatin.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
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Authors and funding
6 authors.
Funding
Abstract
background7-Hydroxymethotrexate (7-OHMTX) is the main metabolite in plasma following high-dose MTX (HD-MTX), which may result in activity and toxicity of the MTX. Moreover, 7-OHMTX could produce crystalline-like deposits within the renal tubules under acidic conditions or induce renal inflammation, oxidative stress, and cell apoptosis through various signaling pathways, ultimately leading to kidney damage. The objectives of this study were thus to explore the exposure-safety relationship of two compounds and search the most reliable marker for predicting HDMTX nephrotoxicity.
methodA total of 280 plasma concentration data (140 for MTX and 140 for 7-OHMTX) for 60 pediatric patients with non-Hodgkin lymphoma (NHL) were prospectively collected. Plasma MTX and 7-OHMTX concentrations were determined using a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method. A nonlinear mixed effect model approach was used to build a joint population pharmacokinetic (PopPK) model. After validation, the model estimated the peak concentration (C
resultsA three-compartment chain model (central and peripheral compartments for MTX and central compartment 7-OHMTX) with the first-order elimination adequately characterized the in vivo process of MTX and 7-OHMTX. The covariate analysis identified that the aspartate aminotransferase (AST) was strongly associated with the peripheral volume of distribution of MTX. Moreover, the C
conclusionsWe demonstrated that the C
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