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 (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.
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Authors | Shuang Liu, Taocui Zhang, Huifang Sun, Lisha Lin, Na Gao, Weili Wang, Sujuan Li, Jinhua Zhao |
Journal | Marine drugs
(Mar Drugs)
Vol. 19
Issue 4
(Apr 11 2021)
ISSN: 1660-3397 [Electronic] Switzerland |
PMID | 33920475
(Publication Type: Journal Article)
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Chemical References |
- Factor Xa Inhibitors
- Glycosaminoglycans
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Topics |
- Animals
- Biotransformation
- Blood Coagulation
(drug effects)
- Drug Monitoring
- Factor Xa Inhibitors
(administration & dosage, isolation & purification, pharmacokinetics)
- Glycosaminoglycans
(administration & dosage, isolation & purification, pharmacokinetics)
- Half-Life
- Holothuria
(metabolism)
- Injections, Intravenous
- Injections, Subcutaneous
- Male
- Partial Thromboplastin Time
- Rats, Sprague-Dawley
- Renal Elimination
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