Trial reportBritish journal of clinical pharmacology2012
Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.
Trial report in British journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Factors influencing methotrexate pharmacokinetics highlight the need for individualized dose adjustment: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- Urinary coproporphyrin I/(I + III) ratio as a surrogate for MRP2 or other transporter activities involved in methotrexate clearance.British journal of clinical pharmacology · 2014Trial
- Population pharmacokinetic model of high-dose methotrexate in Malaysian adults with hematological malignancies.European journal of clinical pharmacology · 2026Article
- A Minimally Invasive, Subcutaneous Biosensor Reliably Estimates Plasma Methotrexate Exposure and Quantifies Plasma-to-Tissue Transport Kinetics.ACS pharmacology & translational science · 2026Article
- Targeted drug monitoring in oncology for personalized treatment with use of next generation analytics.Discover oncology · 2025Review
- Risk factors associated with high-dose methotrexate induced toxicities in primary central nervous system lymphoma.Frontiers in pharmacology · 2025Article
- Population Pharmacokinetic and Toxicity Analysis of High-Dose Methotrexate in Patients with Central Nervous System Lymphoma.Clinical pharmacokinetics · 2025Article
- Clinical decision support for chemotherapy-induced neutropenia using a hybrid pharmacodynamic/machine learning model.CPT: pharmacometrics & systems pharmacology · 2023Article
- High-dose methotrexate and rituximab induction regimen in immunocompetent patients with primary CNS lymphoma: a retrospective single-center study of survival predictors.Journal of neuro-oncology · 2022Article
- Therapeutic drug monitoring for cytotoxic anticancer drugs: Principles and evidence-based practices.Frontiers in oncology · 2022Review
- Prospective evaluation of high-dose methotrexate pharmacokinetics in adult patients with lymphoma using novel determinants of kidney function.Clinical and translational science · 2022Observational
- A minimal physiologically based pharmacokinetic model for high-dose methotrexate.Cancer chemotherapy and pharmacology · 2021Article
- Improvement of outcomes of an escalated high-dose methotrexate-based regimen for patients with newly diagnosed primary central nervous system lymphoma: a real-world cohort study.Cancer management and research · 2021Article
- Comparison of Body Size, Morphomics, and Kidney Function as Covariates of High-Dose Methotrexate Clearance in Obese Adults with Primary Central Nervous System Lymphoma.Pharmacotherapy · 2020Article
- Primary Central Nervous System Lymphoma: Molecular Pathogenesis and Advances in Treatment.Translational oncology · 2019Review
- Clinical significance of polyglutamylation in primary central nervous system lymphoma.Acta neuropathologica communications · 2018Article
- Primary CNS lymphoma.Current hematologic malignancy reports · 2014Review
- Physiologically based pharmacokinetic modelling of methotrexate and 6-mercaptopurine in adults and children. Part 1: methotrexate.Journal of pharmacokinetics and pharmacodynamics · 2014Article
- Advantages of dose-dense methotrexate protocol for primary central nervous system lymphoma: comparison of two different protocols at a single institution.Neurologia medico-chirurgica · 2013Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThere is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h.
methodsA population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four.
resultsThe dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) < 0.5 µmol l(-1) up to -35% in patients with MTX C(24) > 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure.
conclusionsA simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.