Evidence map›Paper›PMID 40453209›Full record

ArticleDrug design, development and therapy2025

Simultaneous Determination of Unbound Plasma Concentration of Methotrexate and 7-Hydroxymethotrexate in Children Patients Receiving High-Dose Methotrexate Therapy.

Wei-Chong Dong, Shuai-Shuai Gao, Bo Shi, Hao-Ran Li, Ye Jiang, Jia-Liang Guo, Zhi-Qing Zhang, Ying-Ze Zhang

Abstract read
In one paragraph

Article in Drug design, development and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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.

Wei-Chong DongDepartment of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, People's Republic of China.ORCID 0000-0003-1605-644X
Shuai-Shuai GaoDepartment of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, People's Republic of China.
Bo ShiDepartment of Orthopaedics, Hebei Medical University Third Hospital, Shijiazhuang, Hebei Province, 050000, People's Republic of China.ORCID 0009-0008-4584-7586
Hao-Ran LiDepartment of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, People's Republic of China.
Ye JiangSchool of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei Province, 050017, People's Republic of China.ORCID 0000-0003-0507-8520
Jia-Liang GuoDepartment of Orthopaedics, Hebei Medical University Third Hospital, Shijiazhuang, Hebei Province, 050000, People's Republic of China.ORCID 0000-0003-3023-1339
Zhi-Qing ZhangDepartment of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, People's Republic of China.
Ying-Ze ZhangThe School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: High-dose methotrexate (HD-MTX) is seen as an effective therapy for acute lymphoblastic leukemia (ALL); however, it is extremely toxic. Monitoring the plasma concentrations of methotrexate (MTX) and its important metabolite, 7-hydroxy-methotrexate (7-OH-MTX), on a routine basis aids in dose modification of rescue medications and in avoiding toxicity. The pharmacologically active and toxic effects of drugs are due to the unbound portion, as most drugs are bound to plasma proteins to some degree. However, the simultaneous measurement of unbound plasma concentrations of MTX and 7-OH-MTX has not been reported. Methods: We developed and validated a hollow fiber centrifugal ultrafiltration (HFCF-UF) technology to simultaneously analyze unbound MTX and 7-OH-MTX concentrations in human plasma. In total, 234 plasma samples from 58 children diagnosed with ALL who were administered HD-MTX were used in our study. We investigated the connection between unbound and total plasma concentrations of MTX and 7-OH-MTX, as well as how these concentrations relate to liver and renal function. Results: The method that was developed is both simple and accurate. A weak linear relationship was observed between the concentrations of unbound and total 7-OH-MTX ( Conclusion: The total concentration of 7-OH-MTX is an unreliable predictor of unbound concentration, necessitating the monitoring of unbound levels. The concentration ratios of 7-OH-MTX to MTX (both total and unbound) could be more accurate and sensitive biomarkers for predicting hepatotoxicity.

Indexed as

Antimetabolites, AntineoplasticMethotrexatePrecursor Cell Lymphoblastic Leukemia-LymphomaAdolescentChildChild, PreschoolDose-Response Relationship, DrugDrug MonitoringFemaleHumansInfantMaleUltrafiltration7-hydroxymethotrexateAntimetabolites, AntineoplasticMethotrexate7-hydroxy-methotrexatehepatotoxicityHFCF-UFmethotrexatenephrotoxicityunbound concentration

Identifiers

PMID40453209
PMCPMC12124301

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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.