SynthesisEuropean journal of drug metabolism and pharmacokinetics2022
A Systematic Review of Population Pharmacokinetic Models of Methotrexate.
Synthesis in European journal of drug metabolism and pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Population pharmacokinetic analyses of methotrexate in pediatric patients: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- Toxicity-Tailored Thresholds of Delayed Methotrexate Elimination in Non-Hodgkin Lymphoma: A Population-Based Approach to Therapy Optimization.European journal of drug metabolism and pharmacokinetics · 2026Article
- Successful re-exposure to high-dose methotrexate after severely delayed methotrexate elimination and renal toxicity in children with acute lymphoblastic leukemia.Haematologica · 2026Article
- GRK2 dysfunction mediates acute kidney injury in murine administered methotrexate combined with omeprazole.Acta pharmacologica Sinica · 2026Article
- Review
- Risk factor identification for delayed excretion in pediatric high-dose methotrexate therapy: a machine learning analysis of real-world data.Frontiers in pharmacology · 2025Article
- Population pharmacokinetics of high-dose methotrexate in patients with primary central nervous system lymphoma.Frontiers in pharmacology · 2025Article
- Population pharmacokinetic model of high-dose methotrexate in Chinese patients with intracranial germ cell tumors.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
- Factors influencing delayed high-dose methotrexate excretion and its correlation with adverse reactions after treatment in children with malignant hematological tumors.Translational pediatrics · 2024Article
- Physiologically based radiopharmacokinetic (PBRPK) modeling to simulate and analyze radiopharmaceutical therapies: studies of non-linearities, multi-bolus injections, and albumin binding.EJNMMI radiopharmacy and chemistry · 2024Article
- Case report: Hepatotoxicity and nephrotoxicity induced by methotrexate in a paediatric patient, what is the role of precision medicine in 2023?Frontiers in pharmacology · 2023Article
- Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response.Pharmaceuticals (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
objectivesMethotrexate (MTX) is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, its toxicity and efficacy varied greatly among individuals, and they could be predicted by its pharmacokinetics. Many population pharmacokinetic models have been published to describe MTX pharmacokinetics. The objective of this systematic review was to summarize and discuss covariates with significant influence on MTX pharmacokinetics.
methodsWe searched PubMed and EMBASE databases from their inception to April 2021 for population pharmacokinetic of MTX. The articles were screened by inclusion and exclusion criteria. The characteristics of studies and information for model construction and validation were extracted, summarized and discussed.
resultsThirty-five articles were included. The two-compartment model well described the pharmacokinetic behavior of MTX. For inter-individual variability, an exponential distribution error model was usually used for high-dose MTX population pharmacokinetic models, while a proportional distribution error model was used for low-dose MTX population pharmacokinetic models. Proportional and combined proportional and additive error models were used to describe residual error. Renal function was an independent indicator of MTX clearance. Body weight, age, gene polymorphisms (SLCO1B1, ABCC2, ABCB1, ABCG2 and MTHFR) and co-medications (proton pump inhibitors, non-steroidal anti-inflammatory drug, dexamethasone, vancomycin, penicillin and salicylic acid) could influence MTX clearance. Body weight, body surface area, age and dosage regimen have significant influence on MTX central compartment volume. Internal bootstrap test, external validation and visual predictive check were used to evaluate model predictive ability.
conclusionsVarious covariates could affect MTX pharmacokinetics, and their relationships have been summarized and discussed. This review will be helpful for researchers to develop their own population pharmacokinetic models and select appropriate models for individualized therapy of MTX.
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Registered trials
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.