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Absorption, distribution, metabolism and excretion of linaprazan glurate in rats

文献类型：期刊论文

作者Zhang, Xinyue2,3; Liu, Donghui2,3; Lu, Ming1; Yuan, Yali2,3; Yang, Chen2; Yang, Ying2; Xiu, Jin1; Hu, Pingsheng1; Zheng, Yuandong2; Diao, Xingxing2,3
刊名JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
出版日期2024-05-15
卷号242页码:10
关键词Linaprazan glurate [14C]linaprazan glurate Linaprazan ADME Radio-labeling P-CAB
ISSN号0731-7085
DOI10.1016/j.jpba.2024.116012
通讯作者Hu, Pingsheng(hups@sinorda.com) ; Zheng, Yuandong(ydzheng@simm.ac.cn) ; Diao, Xingxing(xxdiao@simm.ac.cn)
英文摘要Linaprazan (AZD0865, TX07) is one of potassium-competitive acid blockers. However, linaprazan is rapidly excreted from the body, shortening its acid inhibition property. Linaprazan glurate (X842) is a prodrug of linaprazan with a prolonged inhibitory effect on gastric acid secretion. Linaprazan glurate has entered clinical trials, but few studies have reported its metabolism in non-clinical and clinical settings. In this study, we studied the pharmacokinetics, tissue distribution, mass balance, and metabolism of linaprazan glurate in rats after a single oral dose of 2.4 mg/kg (100 mu Ci/kg) [14C]linaprazan glurate. The results demonstrated that linaprazan glurate was mainly excreted via feces in rats with 70.48% of the dose over 168 h. The plasma AUC0-infinity of linaprazan glurate in female rats was 2 times higher than that in male rats. Drug-related substances were mainly concentrated in the stomach, eyes, liver, small intestine, and large intestine after administration. In blood, drugrelated substances were mostly distributed into plasma instead of hemocytes. In total, 13 metabolites were detected in rat plasma, urine, feces, and bile. M150 (2,6-dimethylbenzoic acid) was the predominant metabolite in plasma, accounting for 80.65% and 67.65% of AUC0-24h in male and female rats, respectively. Based on the structures, linaprazan glurate was mainly hydrolyzed into linaprazan, followed by a series of oxidation, dehydrogenation, and glucuronidation in rats. Besides, CES2 is the main metabolic enzyme involved in the hydrolysis of linaprazan glurate to linaprazan.
WOS关键词PROTON PUMP INHIBITORS ; ACID ; VONOPRAZAN ; POTASSIUM ; ESOMEPRAZOLE ; AZD0865 ; PHARMACOLOGY
资助项目Jiangsu Sinorda Biomedicine Co., Ltd. ; National Key R&D Program of China[2022YFF1202600] ; National Natural Science Foundation of China[82373938] ; National Natural Science Foundation of China[82104275] ; Key Technologies R&D Program of Guangdong Province[2023B1111030004]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001186308800001
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/310366]  
专题中国科学院上海药物研究所
通讯作者Hu, Pingsheng; Zheng, Yuandong; Diao, Xingxing
作者单位1.Jiangsu Sinorda Biomed Co Ltd, Taicang 215400, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201210, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Xinyue,Liu, Donghui,Lu, Ming,et al. Absorption, distribution, metabolism and excretion of linaprazan glurate in rats[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2024,242:10.
APA Zhang, Xinyue.,Liu, Donghui.,Lu, Ming.,Yuan, Yali.,Yang, Chen.,...&Diao, Xingxing.(2024).Absorption, distribution, metabolism and excretion of linaprazan glurate in rats.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,242,10.
MLA Zhang, Xinyue,et al."Absorption, distribution, metabolism and excretion of linaprazan glurate in rats".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 242(2024):10.

入库方式： OAI收割

来源：上海药物研究所

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