Evidence map›Paper›PMID 39039675›Full record

ArticleCurrent drug metabolism2024

Study on Cytochrome P450 Metabolic Profile of Paclitaxel on Rats using QTOF-MS.

Zhaoyang Meng, Junjun Chen, Lingyan Xu, Xiao Xiao, Ling Zong, Yonglong Han, Bo Jiang

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Article in Current drug metabolism, 2024. 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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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Zhaoyang MengDepartment of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yi Shan Road, Shanghai, 200233, P. R. China.
Junjun ChenDepartment of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yi Shan Road, Shanghai, 200233, P. R. China.
Lingyan XuDepartment of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yi Shan Road, Shanghai, 200233, P. R. China.
Xiao XiaoDepartment of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yi Shan Road, Shanghai, 200233, P. R. China.
Ling ZongDepartment of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yi Shan Road, Shanghai, 200233, P. R. China.
Yonglong HanDepartment of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yi Shan Road, Shanghai, 200233, P. R. China.
Bo JiangDepartment of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yi Shan Road, Shanghai, 200233, P. R. China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPaclitaxel (PTX) is a key drug used for chemotherapy for various cancers. The hydroxylation metabolites of paclitaxel are different between humans and rats. Currently, there is little information available on the metabolic profiles of CYP450 enzymes in rats.

objectiveThis study evaluated the dynamic metabolic profiles of PTX and its metabolites in rats and

methodsUltra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and LC-MS/MS were applied to qualitative and quantitative analysis of PTX and its metabolites in rats, liver microsomes and recombinant enzyme CYP3A1/3A2. Ten specific inhibitors [NF (CYP1A1), FFL (CYP1A2), MOP (CYP2A6), OND (CYP2B6), QCT (CYP2C8), SFP (CYP2C9), NKT (CYP2C19), QND (CYP2D6), MPZ (CYP2E1) and KTZ (CYP3A4)] were used to identify the metabolic pathway

resultsFour main hydroxylated metabolites of PTX were identified. Among them, 3'-p-OH PTX and 2-OH PTX were monohydroxylated metabolites identified in rats and liver microsome samples, and 6α-2-di-OH PTX and 6α-5"-di-OH PTX were dihydroxylated metabolites identified in rats. CYP3A recombinant enzyme studies showed that the CYP3A1/3A2 in rat liver microsomes was mainly responsible for metabolizing PTX into 3'-p- OH-PTX and 2-OH-PTX. However, 6α-OH PTX was not detected in rat plasma and liver microsome samples.

conclusionThe results indicated that the CYP3A1/3A2 enzyme, metabolizing PTX into 3'-p-OH-PTX and 2- OH-PTX, is responsible for the metabolic of PTX in rats. The CYP2C8 metabolite 6α-OH PTX in humans was not detected in rat plasma in this study, which might account for the interspecies metabolic differences between rats and humans. This study will provide evidence for drug-drug interaction research in rats.

Indexed as

Cytochrome P-450 Enzyme SystemMicrosomes, LiverPaclitaxelRats, Sprague-DawleyAnimalsAntineoplastic Agents, PhytogenicChromatography, High Pressure LiquidCytochrome P-450 Enzyme InhibitorsMaleRatsTandem Mass SpectrometryAntineoplastic Agents, PhytogenicCytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemPaclitaxel2-hydroxypaclitaxel3'-p-hydroxypaclitaxelCYP3A1/3A2metabolic profilePaclitaxelUHPLC-Q-TOF-MS.

Identifiers

PMID39039675

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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.