Pharmacokinetics and tissue distribution of remdesivir and its metabolites nucleotide monophosphate, nucleotide triphosphate, and nucleoside in mice

doi:10.1038/s41401-020-00537-9

	Pharmacokinetics and tissue distribution of remdesivir and its metabolites nucleotide monophosphate, nucleotide triphosphate, and nucleoside in mice
	Hu, Wen-juan 1; Chang, Lu 1; Yang, Ying 1; Wang, Xin 1; Xie, Yuan-chao 1; Shen, Jing-shan 1; Tan, Bo 2; Liu, Jia 1
刊名	ACTA PHARMACOLOGICA SINICA
	2020-10-12
页码	6
关键词	remdesivir pharmacokinetics tissue distribution nucleotide monophosphate nucleotide triphosphate nucleoside
ISSN号	1671-4083
DOI	10.1038/s41401-020-00537-9
通讯作者	Tan, Bo(tbot@163.com) ; Liu, Jia(jia.liu@simm.ac.cn)
英文摘要	Remdesivir (RDV) exerts anti-severe acute respiratory coronavirus 2 activity following metabolic activation in the target tissues. However, the pharmacokinetics and tissue distributions of the parent drug and its active metabolites have been poorly characterized to date. Blood and tissue levels were evaluated in the current study. After intravenous administration of 20 mg/kg RDV in mice, the concentrations of the parent drug, nucleotide monophosphate (RMP) and triphosphate (RTP), as well as nucleoside (RN), in the blood, heart, liver, lung, kidney, testis, and small intestine were quantified. In blood, RDV was rapidly and completely metabolized and was barely detected at 0.5 h, similar to RTP, while its metabolites RMP and RN exhibited higher blood levels with increased residence times. The area under the concentration versus time curve up to the last measured point in time (AUC(0-t)) values of RMP and RN were 4558 and 136,572 h.nM, respectively. The maximum plasma concentration (C-max) values of RMP and RN were 2896 nM and 35,819 nM, respectively. Moreover, RDV presented an extensive distribution, and the lung, liver and kidney showed high levels of the parent drug and metabolites. The metabolic stabilities of RDV and RMP were also evaluated using lung, liver, and kidney microsomes. RDV showed higher clearances in the liver and kidney than in the lung, with intrinsic clearance (CLint) values of 1740, 1253, and 127 mL/(min.g microsomal protein), respectively.
资助项目	Youth Innovation Promotion Association of the Chinese Academy of Sciences[2016263]
WOS关键词	CARBOXYLESTERASE ; GS-5734 ; PRODRUG ; VIRUS ; EBOLA
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000577055300001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291326]
专题	中国科学院上海药物研究所
通讯作者	Tan, Bo; Liu, Jia
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Clin Pharmacokinet Lab, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Hu, Wen-juan,Chang, Lu,Yang, Ying,et al. Pharmacokinetics and tissue distribution of remdesivir and its metabolites nucleotide monophosphate, nucleotide triphosphate, and nucleoside in mice[J]. ACTA PHARMACOLOGICA SINICA,2020:6.
APA	Hu, Wen-juan.,Chang, Lu.,Yang, Ying.,Wang, Xin.,Xie, Yuan-chao.,...&Liu, Jia.(2020).Pharmacokinetics and tissue distribution of remdesivir and its metabolites nucleotide monophosphate, nucleotide triphosphate, and nucleoside in mice.ACTA PHARMACOLOGICA SINICA,6.
MLA	Hu, Wen-juan,et al."Pharmacokinetics and tissue distribution of remdesivir and its metabolites nucleotide monophosphate, nucleotide triphosphate, and nucleoside in mice".ACTA PHARMACOLOGICA SINICA (2020):6.