Evidence map›Paper›PMID 40348891›Full record

ArticleScientific reports2025

The pharmacokinetic-nephrotoxicity relationships of CMS and CMS-E2 from the perspective of plasma and kidney drug concentrations in rats.

Chenxue Guo, Lin Xi, Xingyi Qu, Zhiwei Huang, Size Li, Wanzhen Li, Xiaofen Liu, Jing Zhang

Abstract read
In one paragraph

Article in Scientific reports, 2025. 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
–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

2 citing papers in PubMed.

  1. Article
  2. Article
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.

Chenxue Guo *Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Lin Xi *Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Xingyi QuInstitute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Zhiwei HuangInstitute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Size LiInstitute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Wanzhen LiInstitute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Xiaofen LiuInstitute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, China. xiaofenliu@fudan.edu.cn.
Jing ZhangInstitute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, China. zhangj61@fudan.edu.cn.

Funding

Major Research and Development Project of Innovative Drugs, Ministry of Science and Technology of China 2017ZX09304005
6 · The paper itself

Abstract

Nephrotoxicity has seriously affected the clinical application of colistin methanesulphonate (CMS). Colistin B methanesulphonate (CMS-E2) is a novel polymyxin developed and aimed to have lower nephrotoxicity. This study aimed to investigate the relationships between pharmacokinetics (PK) and nephrotoxicity of CMS and CMS-E2 and compare the toxicity of the two drugs in rats. Rats were treated intraperitoneally with a single dose of saline, CMS [10, 20 mg/kg of colistin base activity (CBA)], and CMS-E2 (20, 40 mg/kg CBA). An LC-MS/MS method was developed to determine plasma and renal tissue concentrations of CMS/CMS-E2 and colistin/colistin B. The severity of renal injuries was examined both biochemically and histologically. The PK-toxicodynamic (TD) model was evaluated to characterize the PK of CMS/CMS-E2 and colistin/colistin B in plasma as well as its relationship with nephrotoxicity. Creatinine (CR) and blood urea nitrogen (BUN) profiles were described using an indirect link PK-TD model, with linear-effect relationship. Both the slope between colistin or colistin B concentrations in the effect compartment and CR, BUN was significantly lower for CMS-E2 compared with CMS (CR: P = 0.027, BUN: P = 0.043). The concentrations of colistin and colistin B in kidneys were correlated with CR, BUN values, and histologic examination scores. The regression coefficient of CMS-E2 between the colistin B concentrations in renal tissues and CR, BUN values were lower, as well (CR: P = 0.003, BUN: P = 0.001). The renal injuries induced by CMS and CMS-E2 lagged behind the change of plasma colistin or colistin B concentrations and correlated to those in kidneys. CMS-E2 showed significantly lower nephrotoxicity compared to CMS in vivo.

Indexed as

Anti-Bacterial AgentsColistinKidneyAnimalsBlood Urea NitrogenCreatinineMaleRatsRats, Sprague-DawleyTandem Mass SpectrometryAnti-Bacterial AgentsColistinCreatinineColistinColistin BColistin methanesulphonate (CMS)NephrotoxicityPharmacokinetic-toxicodynamicPolymyxins

Identifiers

PMID40348891
PMCPMC12065821

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