ArticleClinical pharmacokinetics2019
The Population Pharmacokinetics of High-Dose Methotrexate in Infants with Acute Lymphoblastic Leukemia Highlight the Need for Bedside Individualized Dose Adjustment: A Report from the Children's Oncology Group.
Article in Clinical pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 5 of them syntheses 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.
The trial behind it
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
20 citing papers in PubMed, 5 syntheses or guidelines pooled it, 37 citations in OpenAlex.
- Population pharmacokinetic analyses of methotrexate in pediatric patients: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- Factors influencing methotrexate pharmacokinetics highlight the need for individualized dose adjustment: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- Extracorporeal Treatment for Methotrexate Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.Clinical journal of the American Society of Nephrology : CJASN · 2022Pooled it
- Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance.European journal of cancer (Oxford, England : 1990) · 2022Pooled it
- A Systematic Review of Population Pharmacokinetic Models of Methotrexate.European journal of drug metabolism and pharmacokinetics · 2022Pooled it
- Application of Pharmacometric Modelling Towards Precise Dosing in Neonates, Infants and Toddlers: A Scoping Review.Clinical pharmacokinetics · 2026Review
- Development and Evaluation of a Population Pharmacokinetic Model for High-Dose Methotrexate in Japanese Pediatric Patients with Acute Lymphoblastic Leukemia.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
- Population Pharmacokinetics and Covariate Analysis of Methotrexate in Pediatric Acute Lymphoblastic Leukemia.Drug design, development and therapy · 2025Article
- Population pharmacokinetics of high-dose methotrexate in patients with primary central nervous system lymphoma.Frontiers in pharmacology · 2025Article
- Understanding hemoglobin contribution to high-dose methotrexate disposition-population pharmacokinetics in pediatric patients with hematological malignancies.European journal of clinical pharmacology · 2024Article
- Therapeutic drug monitoring guidelines in oncology: what do we know and how to move forward? Insights from a systematic review.Therapeutic advances in medical oncology · 2024Review
- Clinical covariates that improve the description of high dose methotrexate pharmacokinetics in a diverse population to inform MTXPK.org.Clinical and translational science · 2023Article
- Population Pharmacokinetic Model of Methotrexate in Brazilian Pediatric Patients with Acute Lymphoblastic Leukemia.Pharmaceutical research · 2023Article
- Precision Oncology by Point-of-Care Therapeutic Drug Monitoring and Dosage Adjustment of Conventional Cytotoxic Chemotherapies: A Perspective.Pharmaceutics · 2023Review
- External Evaluation of Population Pharmacokinetic Models of Methotrexate for Model-Informed Precision Dosing in Pediatric Patients with Acute Lymphoid Leukemia.Pharmaceutics · 2023Article
- Population Pharmacokinetics of High-Dose Methotrexate in Chinese Pediatric Patients With Acute Lymphoblastic Leukemia.Frontiers in pharmacology · 2021Article
- Effect of SLCO1B1 Polymorphisms on High-Dose Methotrexate Clearance in Children and Young Adults With Leukemia and Lymphoblastic Lymphoma.Clinical and translational science · 2021Observational
- MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase.Clinical pharmacology and therapeutics · 2020Article
- Pharmacokinetic basis for dosing high-dose methotrexate in infants and young children with malignant brain tumours.British journal of clinical pharmacology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundInfants with acute lymphoblastic leukemia (ALL) treated with high-dose methotrexate may have reduced methotrexate clearance (CL) due to renal immaturity, which may predispose them to toxicity.
objectiveThe aim of this study was to develop a population pharmacokinetic (PK) model of methotrexate in infants with ALL.
methodsA total of 672 methotrexate plasma concentrations were obtained from 71 infants enrolled in the Children's Oncology Group (COG) Clinical Trial P9407. Infants received methotrexate 4 g/m
resultsMethotrexate was best characterized by a two-compartment model with allometric scaling. Weight was the only covariate included in the final model. The coefficient of variation for interoccasion variability (IOV) on CL was relatively high at 25.4%, compared with the interindividual variability for CL and central volume of distribution (10.7% and 13.2%, respectively). Simulations identified that 21.1% of simulated infants benefitted from bedside dose adjustment, and adjustment of methotrexate doses during infusions can avoid supratherapeutic concentrations.
conclusionInfants treated with high-dose methotrexate demonstrated a relatively high degree of IOV in methotrexate CL. The magnitude of IOV in the CL of methotrexate suggests that use of a bedside algorithm may avoid supratherapeutic methotrexate concentrations resulting from high IOV in methotrexate CL.
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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.