Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from Holothuria fuscopunctata, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods

doi:10.3390/md19040212

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	Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from Holothuria fuscopunctata, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods
	Liu,Shuang ; Zhang,Taocui ; Sun,Huifang ; Lin,Lisha ; Gao,Na ; Wang,Weili ; Li,Sujuan ; Zhao,Jinhua
	2021
发表期刊	MARINE DRUGS
ISSN	1660-3397
卷号	19 期号:4 页码:212
摘要	dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber Holothuria fuscopunctata. As a selective inhibitor of intrinsic Xase (iXase), preclinical study showed it was a promising anticoagulant candidate without obvious bleeding risk. In this work, two bioanalytical methods based on the anti-iXase and activated partial thromboplastin time (APTT) prolongation activities were established and validated to determine dHG-5 concentrations in plasma and urine samples. After single subcutaneous administration of dHG-5 at 5, 9, and 16.2 mg/kg to rats, the time to peak concentration (T-max) was at about 1 h, and the peak concentration (C-max) was 2.70, 6.50, and 10.11 mu g/mL, respectively. The plasma elimination half-life(T-1/2(beta)) was also about 1 h and dHG-5 could be almost completely absorbed after s.c. administration. Additionally, the pharmacodynamics of dHG-5 was positively correlated with its pharmacokinetics, as determined by rat plasma APTT and anti-iXase method, respectively. dHG-5 was mainly excreted by urine as the unchanged parent drug and about 60% was excreted within 48 h. The results suggested that dHG-5 could be almost completely absorbed after subcutaneous injection and the pharmacokinetics of dHG-5 are predictable. Studying pharmacokinetics of dHG-5 could provide valuable information for future clinical studies.
关键词	pharmacokinetics pharmacodynamics anticoagulant fucosylated glycosaminoglycan dHG-5 method validation
DOI	10.3390/md19040212
WOS记录号	WOS:000643213900001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/73027
专题	中国科学院昆明植物研究所
作者单位	1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.South Cent Univ Nationalities, Sch Pharmaceut Sci, Wuhan 430074, Peoples R China
推荐引用方式 GB/T 7714	Liu,Shuang,Zhang,Taocui,Sun,Huifang,et al. Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from Holothuria fuscopunctata, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods[J]. MARINE DRUGS,2021,19(4):212.
APA	Liu,Shuang.,Zhang,Taocui.,Sun,Huifang.,Lin,Lisha.,Gao,Na.,...&Zhao,Jinhua.(2021).Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from Holothuria fuscopunctata, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods.MARINE DRUGS,19(4),212.
MLA	Liu,Shuang,et al."Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from Holothuria fuscopunctata, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods".MARINE DRUGS 19.4(2021):212.

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