ArticleClinical pharmacokinetics2025
Population Pharmacokinetic and Toxicity Analysis of High-Dose Methotrexate in Patients with Central Nervous System Lymphoma.
Article in Clinical pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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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
5 citing papers in PubMed.
- Population pharmacokinetic model of high-dose methotrexate in Malaysian adults with hematological malignancies.European journal of clinical pharmacology · 2026Article
- Development and validation of high-dose methotrexate population pharmacokinetic models to inform clinical decisions on dosing.European journal of clinical pharmacology · 2026Article
- Prevention and Treatment of Acute Kidney Injury Associated with High-Dose Methotrexate.Kidney360 · 2025Review
- Population Pharmacokinetics and Covariate Analysis of Methotrexate in Pediatric Acute Lymphoblastic Leukemia.Drug design, development and therapy · 2025Article
- A rare case of low-dose methotrexate toxicity leading to skin and mucosal toxicity and invasive pulmonary mucormycosis: a case report.Frontiers in pharmacology · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh-dose methotrexate (HD-MTX)-based polychemotherapy is widely used for patients with central nervous system (CNS) lymphoma. The pharmacokinetic (PK) variability and unpredictable occurrence of toxicity remain major concerns in HD-MTX treatment.
objectivesThis study aimed to characterize the population PK of HD-MTX in patients with CNS lymphoma and to identify baseline predictors and exposure thresholds that predict a high risk of nephro- and hepatotoxicity.
methodsRoutinely monitored serum MTX concentrations after intravenous infusion of HD-MTX and MTX dosing information were collected retrospectively. Acute event of toxicity (≥ grade 1) was defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 on the basis of serum creatinine and alanine aminotransferase. A population PK model was developed in NONMEM. Toxicity data were analyzed using a logistic regression model, and potential baseline and exposure-related predictors were investigated.
resultsIn total, 1584 MTX concentrations from 110 patients were available for analysis. A two-compartment population PK model adequately described the data. Estimated glomerular filtration rate (eGFR), treatment regimen, albumin, alkaline phosphatase, and body weight were identified as significant covariates that explain the PK variability of HD-MTX. Baseline eGFR and sex were identified as significant predictors for renal toxicity, and MTX dose (mg/m
conclusionsA population PK model was developed for HD-MTX in patients with CNS lymphoma. The toxicity analysis showed that lower baseline eGFR and male sex, and higher MTX dose are associated with increased risk of acute nephro- and hepatotoxicity, respectively. The proposed exposure thresholds that predict high risk of renal toxicity and the developed models hold the potential to guide HD-MTX dosage individualization and better prevent acute toxicity.
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