ArticleEuropean journal of drug metabolism and pharmacokinetics2026
Toxicity-Tailored Thresholds of Delayed Methotrexate Elimination in Non-Hodgkin Lymphoma: A Population-Based Approach to Therapy Optimization.
Article in European journal of drug metabolism and pharmacokinetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHigh-dose methotrexate (HDMTX) is an essential agent in hematological malignancies, the use of which is complicated by toxicities related to delayed elimination. Existing thresholds to define delayed elimination vary widely, creating inconsistencies in clinical practice.
objectiveThis multicenter retrospective study evaluated adult non-Hodgkin Lymphoma patients from Malaysia to establish a locally relevant delayed elimination threshold and identify factors influencing it.
methodPatients who received HDMTX ≥ 500 mg/m
resultA toxicity-based receiver operating characteristic (ROC) approach identified ≥ 0.2 µmol/L at 48 h as the concentration at which lymphocyte count and alanine aminotransferase (ALT) worsened by 50% and mucositis risk increased nearly threefold. Logistic regression showed increased baseline serum creatinine, decreased baseline albumin, and 24 h infusion duration as factors associated with delayed elimination, while Chinese ethnicity was associated with reduced odd of delayed elimination.
conclusionsThese findings support a population-tailored threshold to better guide supportive management and highlight key predictors that can inform future pharmacokinetic modeling for optimized HDMTX therapy.
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