Absorption, distribution, metabolism, and excretion of [C-14]NBP (3-n-butylphthalide) in rats

doi:10.1016/j.jchromb.2021.122915

	Absorption, distribution, metabolism, and excretion of [C-14]NBP (3-n-butylphthalide) in rats
	Tian, Junjun 1,2; Lei, Peng 2; He, Yifei 2; Zhang, Ning 2; Ge, Xinyu 2; Luo, Liqiang 1; Yan, Shu 2; Diao, Xingxing 2
刊名	JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
	2021-09-01
卷号	1181 页码:9
关键词	3-n-butylphthalide (NBP) [C-14]NBP Pharmacokinetics Tissue distribution Metabolism Mass balance
ISSN号	1570-0232
DOI	10.1016/j.jchromb.2021.122915
通讯作者	Luo, Liqiang(luck@shu.edu.cn) ; Yan, Shu(yanshu@simm.ac.cn) ; Diao, Xingxing(xxdiao@simm.ac.cn)
英文摘要	3-n-Butylphthalide (NBP) has a considerable neuroprotective effect and is currently used for the treatment of ischemic stroke. NBP was launched on the market in 2004. However, information on its metabolism in humans and preclinical animal models is insufficient. Although the metabolism of unradiolabeled NBP in humans has been reported, the quantitative metabolite profile, blood-to-plasma radioactivity concentration ratio (B/P), and tissue distribution of this drug remain unclear. We evaluated the pharmacokinetics, tissue distribution, mass balance, and metabolism of NBP in rats after a single oral dose of 60 mg/kg (100 mu Ci/kg) [C-14]NBP to understand the biotransformation of NBP comprehensively and to provide preclinical drug metabolism data prior to human mass balance studies with [C-14]NBP in the near future. NBP absorption was rapid (T-max = 0.75 h) and declined with a terminal half-life of 9.73 h. In rats, the B/P was 0.63 during the 48 h postdose period, indicating that drug related substances did not tend to be distributed into blood cells. Tissue distribution was determined by using the oxidative combustion method. NBP-related components were widely distributed throughout the body, and high concentrations were detected in the stomach, small intestine, fat, bladder, kidney, liver and ovary. At 168 h after oral administration, the mean cumulative recovered radioactivity was 99.85% of the original dose, and was 85.12% in urine and 14.73% in feces. Metabolite profiles were detected via radiochromatography. A total of 49 metabolites were identified in rat plasma, urine, and feces. The main metabolic pathways were oxidation, glucuronidation, and sulfation. Overall, NBP was absorbed rapidly, distributed throughout the body, and excreted in the form of metabolites. Urine was the main excretion route, and the absorption, distribution, metabolism and excretion of NBP showed no significant gender difference between male and female rats.
资助项目	National Natural Science Foundation of China[81903701]
WOS关键词	RADIOLABELED COMPOUNDS ; LIQUID-CHROMATOGRAPHY ; DRUG-METABOLISM ; HUMAN PLASMA ; MOUSE MODEL ; NBP ; IDENTIFICATION ; 3-HYDROXY-NBP ; DISCOVERY
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000702909800012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297558]
专题	中国科学院上海药物研究所
通讯作者	Luo, Liqiang; Yan, Shu; Diao, Xingxing
作者单位	1.Shanghai Univ, Coll Sci, Dept Chem, Shanghai 200444, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Tian, Junjun,Lei, Peng,He, Yifei,et al. Absorption, distribution, metabolism, and excretion of [C-14]NBP (3-n-butylphthalide) in rats[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2021,1181:9.
APA	Tian, Junjun.,Lei, Peng.,He, Yifei.,Zhang, Ning.,Ge, Xinyu.,...&Diao, Xingxing.(2021).Absorption, distribution, metabolism, and excretion of [C-14]NBP (3-n-butylphthalide) in rats.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,1181,9.
MLA	Tian, Junjun,et al."Absorption, distribution, metabolism, and excretion of [C-14]NBP (3-n-butylphthalide) in rats".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 1181(2021):9.