Evidence map›Paper›PMID 30951714›Full record

ArticleEuropean journal of pharmacology2019

Methotrexate disposition, anti-folate activity and efficacy in the collagen-induced arthritis mouse model.

Rakesh K Singh, Leon van Haandel, Paul Kiptoo, Mara L Becker, Teruna J Siahaan, Ryan S Funk

Open access · greenAbstract read
In one paragraph

Article in European journal of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

14 citing papers in PubMed, 27 citations in OpenAlex.

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  3. Carnitine deficiency augments methotrexate-mediated acute renal injury in rats.Journal of the Egyptian National Cancer Institute · 2025
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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

6 authors at 3 institutions in 1 country.

Rakesh K SinghDepartment of Pharmacy Practice, University of Kansas Medical Center, Kansas City, KS, USA.
Leon van HaandelDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, MO, USA.
Paul KiptooDepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA.
Mara L BeckerDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, MO, USA.
Teruna J SiahaanDepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA.
Ryan S FunkDepartment of Pharmacy Practice, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: ryanfunk@kumc.edu.
Children's Mercy Hospital · USUniversity of Kansas · USUniversity of Kansas Medical Center · US

Funding

Using Integrated Omics to Identify Dysfunctional Genetic Mechanisms Influencing Schizophrenia and Sleep DisturbancesP20GM130423 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Dingran Chang, Steven Allan Soper · 2019 to 2026
$21.5M
Institutional Career Development CoreKL2TR002367 · NCATS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI MATTHEW W MOSCONI, NICOLE L NOLLEN · 2017 to 2026
$7.3M
NRSA Training CoreTL1TR002368 · NCATS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Jennifer Lynn Goldman, NICOLE L NOLLEN · 2017 to 2026
$4.0M
NCATS NIH HHS KL2 TR002367NCATS NIH HHS TL1 TR002368NIGMS NIH HHS P20 GM130423
6 · The paper itself

Abstract

Methotrexate (MTX) efficacy in autoimmune arthritis is variable and unpredictable resulting in the need for the identification of biomarkers to guide drug therapy. This study utilizes the collagen-induced arthritis mouse model to investigate erythrocyte MTX disposition and anti-folate activity as biochemical markers of efficacy in autoimmune arthritis. Following induction of arthritis, DBA/1J mice were treated with once-weekly subcutaneous MTX at varying doses over a period of 40 days. At the completion of the study tissue samples were analyzed for MTX and folate content and assessed for their relationship with MTX efficacy. MTX treatment resulted in a reduction in disease activity that was variable and dose-dependent. Erythrocyte accumulation of MTX and its polyglutamate metabolites were dose proportionate, however, polyglutamate metabolites represented a mean ± S.E.M. of 8.9 ± 0.4% of total erythrocyte MTX, which is markedly lower than previously observed in humans and failed to display any significant association with MTX efficacy. MTX treatment resulted in reductions in erythrocyte 5-methyl-tetrahydrofolate (5mTHF) levels that were similar to those previously observed in human studies. Disease induction was associated with a decrease in liver 5mTHF and increased formyl-tetrahydrofolate (fTHF) that was normalized in MTX treated mice. MTX efficacy was associated with reductions in erythrocyte 5mTHF (P = 0.04) and increases in liver 5mTHF (P = 0.0001). Together, these findings demonstrate a relationship between alterations in tissue folate levels and MTX efficacy, and supports erythrocyte levels of 5mTHF as a marker of MTX efficacy in autoimmune arthritis.

Indexed as

AnimalsArthritis, ExperimentalCollagenDisease Models, AnimalFolic AcidFolic Acid AntagonistsMaleMethotrexateMicePolyglutamic AcidCollagenFolic AcidFolic Acid AntagonistsMethotrexatePolyglutamic AcidArthritisBiomarkersFolatesMethotrexatePharmacodynamicsPharmacokinetics

Identifiers

PMID30951714
PMCPMC6500488
OpenAlexW2934964265

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.