Evidence mapPaperPMID 40460109Full record

ArticlePloS one2025

Drug-drug interactions between epidermal growth factor receptor tyrosine kinase inhibitors and rivaroxaban in vitro and in vivo.

Dongxu Wang, Shuanghu Wang, Hualan Wu, Peiwu Geng, Yang An, Xiaoyue Zhou, Minghui Du, Yuwei Li, Jia Chong, Yingying Li and 7 more

Abstract read
In one paragraph

Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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

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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

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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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

17 authors.

Dongxu WangDepartment of Cardiovascular, Beijing Hospital, National Centre of Gerontology, Beijing, China.
Shuanghu WangLaboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, Zhejing, China.
Hualan WuDepartment of Cardiovascular, Beijing Hospital, National Centre of Gerontology, Beijing, China.
Peiwu GengLaboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, Zhejing, China.
Yang AnDepartment of Cardiovascular, Beijing Hospital, National Centre of Gerontology, Beijing, China.
Xiaoyue ZhouDepartment of Cardiovascular, Beijing Hospital, National Centre of Gerontology, Beijing, China.
Minghui DuDepartment of Cardiovascular, Beijing Hospital, National Centre of Gerontology, Beijing, China.
Yuwei LiDepartment of Cardiovascular, Beijing Hospital, National Centre of Gerontology, Beijing, China.
Jia ChongDepartment of Cardiovascular, Beijing Hospital, National Centre of Gerontology, Beijing, China.
Yingying LiDepartment of Cardiovascular, Beijing Hospital, National Centre of Gerontology, Beijing, China.
Fang WangDepartment of Cardiovascular, Beijing Hospital, National Centre of Gerontology, Beijing, China.
Zebei LuLaboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, Zhejing, China.
Yu WangLaboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, Zhejing, China.
Jiefu YangDepartment of Cardiovascular, Beijing Hospital, National Centre of Gerontology, Beijing, China.
Chuanbao LiDepartment of Clinical Laboratory, Beijing Hospital, National Center of Gerontology, Beijing, China.
Dapeng DaiThe Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Centre of Gerontology, Beijing, China.
Hao ChenDepartment of Cardiovascular, Beijing Hospital, National Centre of Gerontology, Beijing, China.ORCID https://orcid.org/0000-0002-4488-793X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTyrosine kinase inhibitor (TKI) and rivaroxaban co-administration is common for patients with cancer and venous thromboembolism. However, the drug-drug interactions (DDIs) between epidermal growth factor receptor (EGFR) TKIs and rivaroxaban remain uncertain.

methodsDDIs were investigated in vitro and in vivo. In vitro experiments were conducted using rat liver microsomes, and rivaroxaban metabolites were tested to identify the two TKIs that exhibit the most significant DDIs. The type of inhibition was investigated using Lineweaver-Burk plots. For in vivo experiments, eighteen rats were randomly divided into three groups and pretreated with CMC-Na together with avitinib or gefitinib, or with CMC-Na alone for 7 days. On day 8, rivaroxaban was orally administered to each group. Blood samples were collected at various time points, and plasma rivaroxaban was quantified. Molecular docking was performed to explore the mechanism of DDIs.

resultsAvitinib and gefitinib showed the most potent inhibitory effects among multiple EGFR TKIs and inhibited rivaroxaban metabolism in a mixed model of noncompetitive and uncompetitive inhibition. The area under the drug-time curve and maximum plasma concentration of rivaroxaban were significantly higher following avitinib and gefitinib pretreatment, while the apparent volume of distribution and clearance rates were significantly lower. Our molecular docking analysis revealed that these two drugs may inhibit rivaroxaban metabolism by overlapping with its binding site on CYP3A4 and CYP2D6.

conclusionThese findings confirm the presence of DDIs between EGFR TKIs and rivaroxaban. Avitinib and gefitinib significantly inhibit rivaroxaban metabolism, and their co-administration may aggravate the risk of bleeding.

Indexed as

ErbB ReceptorsProtein Kinase InhibitorsRivaroxabanAnimalsDrug InteractionsGefitinibMaleMicrosomes, LiverMolecular Docking SimulationQuinazolinesRatsRats, Sprague-DawleyTyrosine Kinase InhibitorsErbB ReceptorsGefitinibProtein Kinase InhibitorsQuinazolinesRivaroxabanTyrosine Kinase Inhibitors

Identifiers

PMID40460109
PMCPMC12133000

What Socratic holds

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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 Socratic graph.