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

doi:10.3390/md19040212

KIB OpenIR

	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
Source Publication	MARINE DRUGS
ISSN	1660-3397
Volume	19 Issue:4 Pages:212
Abstract	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.
Keyword	pharmacokinetics pharmacodynamics anticoagulant fucosylated glycosaminoglycan dHG-5 method validation
DOI	10.3390/md19040212
WOS ID	WOS:000643213900001
Citation statistics
Document Type	期刊论文
Identifier	http://ir.kib.ac.cn/handle/151853/73027
Collection	中国科学院昆明植物研究所
Affiliation	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
Recommended Citation 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.

Files in This Item:
There are no files associated with this item.

If you have any objections to this item, please fill out the form below and the administrator will contact you as soon as possible.
Content:
Email：	*
Institution:
Verification Code:	Refresh

Any comments and suggestions are welcomed.
Title:	*
Content:
Email：	*
Verification Code:	Refresh

中国科学院昆明植物研究所知识管理系统