Trial reportClinical pharmacokinetics2014
Assessment of the relationship between methotrexate polyglutamates in red blood cells and clinical response in patients commencing methotrexate for rheumatoid arthritis.
Trial report in Clinical pharmacokinetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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.
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
10 citing papers in PubMed, 20 citations in OpenAlex.
- Assessment of Erythrocytes Methotrexate Polyglutamate Three Levels in Psoriatic Patients Treated with Methotrexate Monotherapy and Their Association with Disease Response.Indian journal of clinical biochemistry : IJCB · 2025Article
- Therapeutic Drug Monitoring of Low Methotrexate Doses for Drug Exposure and Adherence Assessment-Pre-Analytical Variables, Bioanalytical Issues, and Current Clinical Applications.International journal of molecular sciences · 2024Review
- Article
- Methotrexate Polyglutamates Analysis by Chromatography Methods in Biological Matrices: A Review.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2021Review
- Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study.Open access rheumatology : research and reviews · 2021Article
- Treatment Options for Resistant Kawasaki Disease.Paediatric drugs · 2018Review
- Population Pharmacokinetics of Intravenous Methotrexate in Patients with Hematological Malignancies: Utilization of Routine Clinical Monitoring Parameters.European journal of drug metabolism and pharmacokinetics · 2017Article
- Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence.Mediators of inflammation · 2017Review
- Folate metabolic pathway single nucleotide polymorphisms: a predictive pharmacogenetic marker of methotrexate response in Indian (Asian) patients with rheumatoid arthritis.Pharmacogenomics · 2015Article
- Simplification of a pharmacokinetic model for red blood cell methotrexate disposition.European journal of clinical pharmacology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesTherapeutic drug monitoring in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX, MTXGlu1) has not been established. In this study, we aim to explore the relationship between red blood cell (RBC) concentrations of MTX and its polyglutamate metabolites (MTXGlu(n); n = 2, 3, 4, 5) and clinical response in RA patients commencing MTX.
methodsThe binding activity of MTXGlu(n) to three putative enzymes involved in the MTX mechanism of action—dihydrofolate reductase, thymidylate synthase, and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase—was simulated. RBC MTXGlu(n) concentrations that gave the highest inhibition activity across all three enzymes were linked with the disease activity score DAS28-3v (C-reactive protein [CRP]). A population pharmacokinetic-pharmacodynamic model was developed to describe the relationship between RBC MTX polyglutamate concentrations and clinical response in 12 RA patients commencing MTX.
resultsThe highest inhibition activity was with RBC MTXGlu(3-5). These polyglutamates were further evaluated for their relationship with DAS28-3v (CRP). Three of the 12 patients had a high DAS28-3v (CRP) at baseline (mean = 6.1) and showed a delayed response to MTX treatment. The remaining nine patients with a lower DAS28-3v (CRP) baseline (mean = 3.6) showed an immediate response. The developed MTX pharmacokinetic-pharmacodynamic model provided an acceptable description of the observed DAS28-3v (CRP) across all patients.
conclusionsThe developed model describes a longitudinal relationship between RBC MTXGlu(3-5) concentrations and DAS28-3v (CRP) in patients with RA commencing MTX. Further work is required to determine whether measurement of RBC MTX polyglutamates might be useful for dose individualisation in patients with RA.
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