Evidence map›Paper›PMID 37667147›Full record

ArticlePharmaceutical research2023

Elucidation of Carboxylesterase Mediated Pharmacokinetic Interactions between Irinotecan and Oroxylin A in Rats via Physiologically Based Pharmacokinetic Modeling.

Jun Zhang, Yufeng Zhang, Yuen Sze Lai, Qianbo Song, Min Xiao, Xiaoyu Ji, Xiaoyu Yan, Zhong Zuo

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 36% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Review
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 at 1 institution in 1 country.

Jun Zhang *School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.
Yufeng Zhang *School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.
Yuen Sze LaiSchool of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.
Qianbo SongSchool of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.
Min XiaoSchool of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.
Xiaoyu JiSchool of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.
Xiaoyu YanSchool of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.
Zhong ZuoSchool of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR. joanzuo@cuhk.edu.hk.
Chinese University of Hong Kong · CN

Funding

Research Grants Council, University Grants Committee 14108119
6 · The paper itself

Abstract

purposeOur previous screening studies identified Oroxylin A (OXA) as a strong inhibitor on the carboxyolesterase mediated hydrolysis of irinotecan to SN-38. The current study employed a whole-body physiologically based pharmacokinetic (PBPK) modeling approach to investigate the underlying mechanisms of the carboxylesterase-mediated pharmacokinetics interactions between irinotecan and OXA in rats.

methodsFirstly, rats received irinotecan intravenous treatment at 35 μmol/kg without or with oral OXA pretreatment (2800 μmol/kg) daily for 5 days. On day 5, blood and tissues were collected for analyses of irinotecan/SN-38 concentrations and carboxylesterase expression. In addition, effects of OXA on the enzyme kinetics of irinotecan hydrolysis and unbound fractions of irinotecan and SN-38 in rat plasma, liver and intestine were also determined. Finally, a PBPK model that integrated the physiological parameters, enzyme kinetics, and physicochemical properties of irinotecan and OXA was developed.

resultsOur PBPK model could accurately predict the pharmacokinetic profiles of irinotecan/SN-38, with AUC

conclusionA whole-body PBPK model was successfully developed to not only predict the impact of oral OXA pretreatment on the pharmacokinetics profiles of irinotecan but also reveal its inhibition on the intestinal carboxylesterase as the major underlying mechanism.

Indexed as

FlavonoidsLiverAnimalsCamptothecinIntestinesIrinotecanRats5,7-dihydroxy-6-methoxy-2-phenylchromen-4-oneCamptothecinFlavonoidsIrinotecancarboxylesteraseirinotecanoroxylin APBPK

Identifiers

PMID37667147
OpenAlexW4386438526

What OpenQuestion holds

Textmetadata
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.