Evidence map›Paper›PMID 39138788›Full record

ArticlePharmaceutical research2024

Fecal SN-38 Content as a Surrogate Predictor of Intestinal SN-38 Exposure and Associated Irinotecan-induced Severe Delayed-Onset Diarrhea by a Novel Use of the Spectrofluorimetric Method.

Zicong Zheng, Vesna Tumbas Šaponjac, Rashim Singh, Jie Chen, Songpol Srinual, Taijun Yin, Rongjin Sun, Ming Hu

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In one paragraph

Article in Pharmaceutical research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
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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

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Zicong ZhengDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA.
Vesna Tumbas ŠaponjacDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA.
Rashim SinghDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA.
Jie ChenDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA.
Songpol SrinualDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA.
Taijun YinDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA.
Rongjin SunDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA. rsun5@central.uh.edu.
Ming HuDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA. mhu4@central.uh.edu.ORCID http://orcid.org/0000-0002-2744-6294

Funding

Mechanistic and Pharmacokinetic Studies of Classical Chinese Formula Xiao Chai Hu Tang Against Irinotecan-Induced Gut ToxicitiesR01CA246209 · NCI · UNIVERSITY OF HOUSTON · PI HU, MING · 2020 to 2024
$978k
Development of Novel Herbal Therapy for Prevention of Irinotecan-induced Severe Delayed Onset DiarrheaR43AT011165 · NCCIH · SANARENTERO LLC · PI SINGH, RASHIM · 2020 to 2021
$377k
National Institute of Health 1R41CA261292-01NCCIH NIH HHS R43 AT011165NCI NIH HHS 5R01CA246209NCI NIH HHS R01 CA246209
6 · The paper itself

Abstract

backgroundIrinotecan administration can lead to severe delayed-onset diarrhea (SDOD) in clinical practice. Currently, there is no reliable surrogate predictor of intestinal exposure to SN-38 and subsequent diarrhea incidence.

methodsThe relationship between fecal 7-ethyl-10-hydroxycamptothecin (SN-38) content and SDOD was investigated in Fisher 344 rats using a novel spectrofluorimetric method. Additionally, a pharmacokinetic study of irinotecan was performed to evaluate the biodistribution of SN-38 to establish the relationship between tissue and fecal SN-38 exposure.

resultsThe spectrofluorimetric method was successfully employed to measure fecal SN-38 and CPT-11 content from Day 3 to Day 6 post-irinotecan administration. Only fecal SN-38 content on Day 3 exhibited a significantly positive correlation with SDOD incidence on Days 4 and 5. A cutoff value of SN-38 ≥ 0.066 mg/g in feces was identified, predicting severe diarrhea incidence with 81% accuracy and 80% specificity. The positive correlation between fecal SN-38 content and SN-38 exposure in the ileum on Day 3 was also reflected in the changes of indicators during intestinal injury, such as prostaglandin E2 level and antioxidant activity.

conclusionFecal SN-38 content proves to be representative of intestinal exposure to SN-38, indicative of intestinal injury, and predictive of SDOD incidence in rats, while the spectrofluorimetric method demonstrates the translational potential.

Indexed as

CamptothecinDiarrheaFecesIrinotecanRats, Inbred F344AnimalsAntineoplastic Agents, PhytogenicIntestinal MucosaMaleRatsSpectrometry, FluorescenceTissue DistributionAntineoplastic Agents, PhytogenicCamptothecinIrinotecanchemotherapy-induced diarrheafecesintestinal drug exposureintestinal toxicityprediction

Identifiers

PMID39138788

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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.