Evidence map›Paper›PMID 34637107›Full record

ArticleEuropean journal of drug metabolism and pharmacokinetics2022

Plasma Distribution of Methotrexate and Its Polyglutamates in Pediatric Acute Lymphoblastic Leukemia: Preliminary Insights.

Ivana Rajšić, Slavica Lazarević, Maja Đanić, Hani Al-Salami, Armin Mooranian, Saša Vukmirović, Momir Mikov, Svetlana Goločorbin-Kon

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In one paragraph

Article 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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Ivana RajšićDepartment of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000, Novi Sad, Serbia.
Slavica LazarevićDepartment of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000, Novi Sad, Serbia. slavica_vukoje@yahoo.com.ORCID http://orcid.org/0000-0002-8191-4095
Maja ĐanićDepartment of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000, Novi Sad, Serbia.
Hani Al-SalamiBiotechnology and Drug Development Research Laboratory, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
Armin MooranianBiotechnology and Drug Development Research Laboratory, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
Saša VukmirovićDepartment of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000, Novi Sad, Serbia.
Momir MikovDepartment of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000, Novi Sad, Serbia.
Svetlana Goločorbin-KonDepartment of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000, Novi Sad, Serbia.
University of Novi Sad · RSCurtin University · AU

Funding

H2020 Marie Skłodowska-Curie Actions 690876ministarstvo prosvete, nauke i tehnološkog razvoja 41012
6 · The paper itself

Abstract

BACKGROUND AND

objectiveHigh-dose methotrexate (HD-MTX) is the mainstream therapy of current acute lymphoblastic leukemia (ALL) regimens, but frequent intra- and interindividual differences in the clinical response to HD-MTX lead to chemotherapeutic interruption or discontinuation. The exact mechanism of transport across the cell membrane and the disposition of active methotrexate metabolites-methotrexate polyglutamates (MTXPGs)-are not well described in the literature. The aim of this study was to gain more insight into the plasma distribution of methotrexate and MTXPGs in pediatric patients with ALL and to clarify the obscure pathways of MTXPGs.

methodsWe prospectively measured the concentrations of MTXPG

resultsNoticeable plasma concentrations of MTXPGs with a 2.2-fold interpatient variability were detected. The highest interindividual variability in total plasma MTXPG concentration was observed at 36 h, and ranged from 13.78 to 30.82 μmol/L. Among all patients, the predominant polyglutamate types in relation to the total plasma MTXPG concentration at each time point were MTXPG

conclusionThe presence of MTXPGs in plasma of patients with ALL could be related to the action of ABC efflux transporters on blood cells and hepatocytes resulting from the administration of high doses of methotrexate. This study may not draw definitive conclusions, but it does reduce uncertainty about the dynamics of methotrexate and its active metabolites, which may be of vital importance for achieving a clinical response.

Indexed as

Antimetabolites, AntineoplasticChildChromatography, LiquidHumansMaleMethotrexatePlasmaPolyglutamic AcidPrecursor Cell Lymphoblastic Leukemia-LymphomaProspective StudiesAntimetabolites, AntineoplasticMethotrexatePolyglutamic Acid

Identifiers

PMID34637107
OpenAlexW3205864849

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Registered trials

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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.