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

by 1,2,†, 1,2,†, 1,2, 1,2, 3, 1,2, 1,2 and 3,*
1
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China
2
University of Chinese Academy of Sciences, Beijing 100049, China
3
School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Alexander N. Shikov
Mar. Drugs 2021, 19(4), 212; https://doi.org/10.3390/md19040212
Received: 17 March 2021 / Revised: 5 April 2021 / Accepted: 5 April 2021 / Published: 11 April 2021
(This article belongs to the Special Issue Pharmaceutical Formulation of Marine Drugs)
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 (Tmax) was at about 1 h, and the peak concentration (Cmax) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(T1/2β) 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. View Full-Text
Keywords: pharmacokinetics; pharmacodynamics; anticoagulant; fucosylated glycosaminoglycan; dHG-5; method validation pharmacokinetics; pharmacodynamics; anticoagulant; fucosylated glycosaminoglycan; dHG-5; method validation
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MDPI and ACS Style

Liu, S.; Zhang, T.; Sun, H.; Lin, L.; Gao, N.; Wang, W.; Li, S.; Zhao, J. Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from Holothuria fuscopunctata, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods. Mar. Drugs 2021, 19, 212. https://doi.org/10.3390/md19040212

AMA Style

Liu S, Zhang T, Sun H, Lin L, Gao N, Wang W, Li S, Zhao J. Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from Holothuria fuscopunctata, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods. Marine Drugs. 2021; 19(4):212. https://doi.org/10.3390/md19040212

Chicago/Turabian Style

Liu, Shuang, Taocui Zhang, Huifang Sun, Lisha Lin, Na Gao, Weili Wang, Sujuan Li, and Jinhua Zhao. 2021. "Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from Holothuria fuscopunctata, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods" Marine Drugs 19, no. 4: 212. https://doi.org/10.3390/md19040212

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