罗库溴铵在人胆汁中的代谢产物分析和转运机制研究  被引量:2

Analysis of metabolites of rocuronium bromide in human bile and the study of transmembrane transport mechanism

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作  者:周爱南 郭子涛 陈佳骏[2] 罗运权[2] 谭波[2] 刁星星 钟大放 ZHOU Ai-nan;GUO Zi-tao;CHEN Jia-jun;LUO Yun-quan;TAN Bo;DIAO Xing-xing;ZHONG Da-fang(Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区:[1]中国科学院上海药物研究所,上海201203 [2]上海中医药大学附属曙光医院,上海201203

出  处:《药学学报》2022年第8期2461-2470,共10页Acta Pharmaceutica Sinica

摘  要:罗库溴铵是一种乙酰胆碱N2受体拮抗剂,为全身麻醉辅助用药。已有文献报道罗库溴铵在体内存在N-去烷基化和去乙酰化两种可能代谢途径,并主要以原形经肝脏摄取和胆汁排泄。本文采用UHPLC-QE-Orbitrap-MS法检测罗库溴铵在人胆汁中的代谢产物,共检测到13种代谢产物,包括I相代谢产物11种,II相代谢产物2种,其中11种为首次报道的代谢产物,罗库溴铵在人体内的主要代谢途径包括去乙酰化、内酰胺化、N-去烷基化、O-去烷基化、羟基化、乙酰化及葡萄糖醛酸化等。采用过表达转运体的HEK293细胞探索罗库溴铵的肝脏跨膜转运机制,结果显示其为肝脏转运体MATE1、OCT1、OATP1B1和OATP1B3的底物。上述研究结果丰富了罗库溴铵体内代谢途径,提出了肝脏摄取和胆汁排泄的可能转运机制,可更好地指导临床精准安全用药。本研究中人体胆汁样本的采集是由上海中医药大学附属曙光医院伦理委员会批准(批件号:2019-775-130-01)。Rocuronium bromide is an acetylcholine N2 receptor antagonist,which can be used as an auxiliary drug for general anesthesia.It has been reported that rocuronium has two possible metabolic pathways:N-dealkylation and O-deacetylation,which are mainly taken up by liver and excreted by bile in the form of primary drugs.In this paper,the metabolites of rocuronium in human bile were detected by UHPLC-QE-orbitrap-MS,thirteen metabolites were detected,including eleven phase I metabolites and two phase II metabolites,eleven of which had not been previously reported.At the same time,HEK293 cells overexpressing transporter were used to explore the transmembrane transport mechanism of rocuronium,the results showed that rocuronium was the substrate of MATE1,OCT1,OATP1B1 and OATP1B3.The above research results enrich the metabolic pathway of rocuronium in vivo,and put forward the possible transport mechanism of liver uptake and bile excretion,which can better guide the accurate and safe clinical drug application.The collection of human bile samples in this study was approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine(Approval Number:2019-775-130-01).

关 键 词:代谢产物 罗库溴铵 人胆汁 UHPLC-QE-orbitrap-MS 转运体 

分 类 号:R917[医药卫生—药物分析学]

 

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