Effects of long-term alcohol exposure on the pharmacokinetic profiles of ketamine and norketamine in rats

doi:10.1016/j.alcohol.2021.01.008

科研成果详情

题名	Effects of long-term alcohol exposure on the pharmacokinetic profiles of ketamine and norketamine in rats
作者	Ying, Lili 1; Chen, Yuyan2; Zhong, Zuoquan2; Wu, Yajin 2; Hu, Lufeng3; Wen, Congcong 2
发表日期	2021-11
发表期刊	ALCOHOL 影响因子和分区
语种	英语
原始文献类型	Article
关键词	alcohol ketamine pharmacokinetics rat UPLC-MS MS
其他关键词	LIVER-DISEASE ; CYTOCHROME-P450 ; ETHANOL ; INDUCTION ; ISOFORMS ; PLASMA ; OCCURS
摘要	Background: Alcohol abuse has become a serious health issue worldwide. Ketamine can reduce addiction risk among patients with alcohol use disorders. This study aimed to determine the effects of alcohol on the pharmacokinetics of ketamine during long-term alcohol exposure. Method: An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of ketamine and norketamine was developed and validated. A total of 15 rats were given 40% alcohol for 3 weeks. The pharmacokinetics of ketamine were measured at time zero, 1 week, 2 weeks, and 3 weeks after alcohol exposure. The metabolic capability of liver CYP450 was evaluated using three probe drugs: metoprolol, phenacetin, and tolbutamide. Results: During drinking of 40% alcohol, the AUC(0-t), AUC(0-infinity), and Cmax of ketamine and norketamine significantly increased, while V and CL significantly decreased with time (p < 0.001). The pharmacokinetic changes of norketamine were highly consistent with ketamine. Additionally, the concentration ratio of norketamine/ketamine in sample time also decreased over time. However, there were no pharmacokinetic changes of three probe drugs, which indicated there was no significant change of liver CYPs activities. Conclusion: Alcohol significantly increases plasma concentration of ketamine and norketamine. The effect of alcohol on pharmacokinetics of ketamine should be considered in clinical therapy. (c) 2021 Published by Elsevier Inc.
资助项目	National Natural Sci-ence Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81701314]
出版者	ELSEVIER SCIENCE INC
出版地	NEW YORK
ISSN	0741-8329
EISSN	1873-6823
卷号	96 页码:55-61
DOI	10.1016/j.alcohol.2021.01.008
页数	7
WOS类目	Substance Abuse ; Pharmacology & Pharmacy ; Toxicology
WOS研究方向	Substance Abuse ; Pharmacology & Pharmacy ; Toxicology
WOS记录号	WOS:000709481400006
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	33549609
SCOPUSEID	2-s2.0-85114405933
通讯作者地址	[Hu, Lufeng]Department of Pharmacy,The First Affiliated Hospital of Wenzhou Medical University,Ouhai District,Wenzhou,325000,China ; [Wen, Congcong]Laboratory Animal Center,Wenzhou Medical University,Ouhai District,Wenzhou,325035,China
Scopus学科分类	Health (social science);Biochemistry;Toxicology;Neurology;Behavioral Neuroscience
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/1172
专题	附属第一医院实验动物中心附属第一医院_药学部药学部
通讯作者	Hu, Lufeng; Wen, Congcong
作者单位	1.Department of Pathology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.Laboratory Animal Center,Wenzhou Medical University,Wenzhou,325035,China; 3.Department of Pharmacy,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 实验动物中心
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Ying, Lili,Chen, Yuyan,Zhong, Zuoquan,et al. Effects of long-term alcohol exposure on the pharmacokinetic profiles of ketamine and norketamine in rats[J]. ALCOHOL,2021,96:55-61.
APA	Ying, Lili, Chen, Yuyan, Zhong, Zuoquan, Wu, Yajin, Hu, Lufeng, & Wen, Congcong. (2021). Effects of long-term alcohol exposure on the pharmacokinetic profiles of ketamine and norketamine in rats. ALCOHOL, 96, 55-61.
MLA	Ying, Lili,et al."Effects of long-term alcohol exposure on the pharmacokinetic profiles of ketamine and norketamine in rats".ALCOHOL 96(2021):55-61.