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

dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber <i<Holothuria fuscopunctata</i<. 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...
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Autor*in:	Shuang Liu [verfasserIn] Taocui Zhang [verfasserIn] Huifang Sun [verfasserIn] Lisha Lin [verfasserIn] Na Gao [verfasserIn] Weili Wang [verfasserIn] Sujuan Li [verfasserIn] Jinhua Zhao [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	pharmacokinetics pharmacodynamics anticoagulant fucosylated glycosaminoglycan dHG-5 method validation

Übergeordnetes Werk:	In: Marine Drugs - MDPI AG, 2005, 19(2021), 4, p 212
Übergeordnetes Werk:	volume:19 ; year:2021 ; number:4, p 212

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/md19040212

Katalog-ID:	DOAJ031401686

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520			\|a dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber <i<Holothuria fuscopunctata</i<. 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 (<i<T<sub<max</sub<</i<) was at about 1 h, and the peak concentration (<i<C<sub<max</sub<</i<) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(<i<T<sub<1/2</sub<<sub<β</sub<</i<) 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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allfields	10.3390/md19040212 doi (DE-627)DOAJ031401686 (DE-599)DOAJfc90d4fc6651418fad8c51346ae37204 DE-627 ger DE-627 rakwb eng QH301-705.5 Shuang Liu verfasserin aut Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from <i<Holothuria fuscopunctata</i<, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber <i<Holothuria fuscopunctata</i<. 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 (<i<T<sub<max</sub<</i<) was at about 1 h, and the peak concentration (<i<C<sub<max</sub<</i<) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(<i<T<sub<1/2</sub<<sub<β</sub<</i<) 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. pharmacokinetics pharmacodynamics anticoagulant fucosylated glycosaminoglycan dHG-5 method validation Biology (General) Taocui Zhang verfasserin aut Huifang Sun verfasserin aut Lisha Lin verfasserin aut Na Gao verfasserin aut Weili Wang verfasserin aut Sujuan Li verfasserin aut Jinhua Zhao verfasserin aut In Marine Drugs MDPI AG, 2005 19(2021), 4, p 212 (DE-627)477992420 (DE-600)2175190-0 16603397 nnns volume:19 year:2021 number:4, p 212 https://doi.org/10.3390/md19040212 kostenfrei https://doaj.org/article/fc90d4fc6651418fad8c51346ae37204 kostenfrei https://www.mdpi.com/1660-3397/19/4/212 kostenfrei https://doaj.org/toc/1660-3397 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2021 4, p 212
spelling	10.3390/md19040212 doi (DE-627)DOAJ031401686 (DE-599)DOAJfc90d4fc6651418fad8c51346ae37204 DE-627 ger DE-627 rakwb eng QH301-705.5 Shuang Liu verfasserin aut Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from <i<Holothuria fuscopunctata</i<, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber <i<Holothuria fuscopunctata</i<. 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 (<i<T<sub<max</sub<</i<) was at about 1 h, and the peak concentration (<i<C<sub<max</sub<</i<) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(<i<T<sub<1/2</sub<<sub<β</sub<</i<) 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. pharmacokinetics pharmacodynamics anticoagulant fucosylated glycosaminoglycan dHG-5 method validation Biology (General) Taocui Zhang verfasserin aut Huifang Sun verfasserin aut Lisha Lin verfasserin aut Na Gao verfasserin aut Weili Wang verfasserin aut Sujuan Li verfasserin aut Jinhua Zhao verfasserin aut In Marine Drugs MDPI AG, 2005 19(2021), 4, p 212 (DE-627)477992420 (DE-600)2175190-0 16603397 nnns volume:19 year:2021 number:4, p 212 https://doi.org/10.3390/md19040212 kostenfrei https://doaj.org/article/fc90d4fc6651418fad8c51346ae37204 kostenfrei https://www.mdpi.com/1660-3397/19/4/212 kostenfrei https://doaj.org/toc/1660-3397 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2021 4, p 212
allfields_unstemmed	10.3390/md19040212 doi (DE-627)DOAJ031401686 (DE-599)DOAJfc90d4fc6651418fad8c51346ae37204 DE-627 ger DE-627 rakwb eng QH301-705.5 Shuang Liu verfasserin aut Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from <i<Holothuria fuscopunctata</i<, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber <i<Holothuria fuscopunctata</i<. 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 (<i<T<sub<max</sub<</i<) was at about 1 h, and the peak concentration (<i<C<sub<max</sub<</i<) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(<i<T<sub<1/2</sub<<sub<β</sub<</i<) 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. pharmacokinetics pharmacodynamics anticoagulant fucosylated glycosaminoglycan dHG-5 method validation Biology (General) Taocui Zhang verfasserin aut Huifang Sun verfasserin aut Lisha Lin verfasserin aut Na Gao verfasserin aut Weili Wang verfasserin aut Sujuan Li verfasserin aut Jinhua Zhao verfasserin aut In Marine Drugs MDPI AG, 2005 19(2021), 4, p 212 (DE-627)477992420 (DE-600)2175190-0 16603397 nnns volume:19 year:2021 number:4, p 212 https://doi.org/10.3390/md19040212 kostenfrei https://doaj.org/article/fc90d4fc6651418fad8c51346ae37204 kostenfrei https://www.mdpi.com/1660-3397/19/4/212 kostenfrei https://doaj.org/toc/1660-3397 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2021 4, p 212
allfieldsGer	10.3390/md19040212 doi (DE-627)DOAJ031401686 (DE-599)DOAJfc90d4fc6651418fad8c51346ae37204 DE-627 ger DE-627 rakwb eng QH301-705.5 Shuang Liu verfasserin aut Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from <i<Holothuria fuscopunctata</i<, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber <i<Holothuria fuscopunctata</i<. 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 (<i<T<sub<max</sub<</i<) was at about 1 h, and the peak concentration (<i<C<sub<max</sub<</i<) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(<i<T<sub<1/2</sub<<sub<β</sub<</i<) 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. pharmacokinetics pharmacodynamics anticoagulant fucosylated glycosaminoglycan dHG-5 method validation Biology (General) Taocui Zhang verfasserin aut Huifang Sun verfasserin aut Lisha Lin verfasserin aut Na Gao verfasserin aut Weili Wang verfasserin aut Sujuan Li verfasserin aut Jinhua Zhao verfasserin aut In Marine Drugs MDPI AG, 2005 19(2021), 4, p 212 (DE-627)477992420 (DE-600)2175190-0 16603397 nnns volume:19 year:2021 number:4, p 212 https://doi.org/10.3390/md19040212 kostenfrei https://doaj.org/article/fc90d4fc6651418fad8c51346ae37204 kostenfrei https://www.mdpi.com/1660-3397/19/4/212 kostenfrei https://doaj.org/toc/1660-3397 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2021 4, p 212
allfieldsSound	10.3390/md19040212 doi (DE-627)DOAJ031401686 (DE-599)DOAJfc90d4fc6651418fad8c51346ae37204 DE-627 ger DE-627 rakwb eng QH301-705.5 Shuang Liu verfasserin aut Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from <i<Holothuria fuscopunctata</i<, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber <i<Holothuria fuscopunctata</i<. 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 (<i<T<sub<max</sub<</i<) was at about 1 h, and the peak concentration (<i<C<sub<max</sub<</i<) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(<i<T<sub<1/2</sub<<sub<β</sub<</i<) 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. pharmacokinetics pharmacodynamics anticoagulant fucosylated glycosaminoglycan dHG-5 method validation Biology (General) Taocui Zhang verfasserin aut Huifang Sun verfasserin aut Lisha Lin verfasserin aut Na Gao verfasserin aut Weili Wang verfasserin aut Sujuan Li verfasserin aut Jinhua Zhao verfasserin aut In Marine Drugs MDPI AG, 2005 19(2021), 4, p 212 (DE-627)477992420 (DE-600)2175190-0 16603397 nnns volume:19 year:2021 number:4, p 212 https://doi.org/10.3390/md19040212 kostenfrei https://doaj.org/article/fc90d4fc6651418fad8c51346ae37204 kostenfrei https://www.mdpi.com/1660-3397/19/4/212 kostenfrei https://doaj.org/toc/1660-3397 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2021 4, p 212
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author	Shuang Liu
spellingShingle	Shuang Liu misc QH301-705.5 misc pharmacokinetics misc pharmacodynamics misc anticoagulant misc fucosylated glycosaminoglycan misc dHG-5 misc method validation misc Biology (General) Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from <i<Holothuria fuscopunctata</i<, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods
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topic_title	QH301-705.5 Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from <i<Holothuria fuscopunctata</i<, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods pharmacokinetics pharmacodynamics anticoagulant fucosylated glycosaminoglycan dHG-5 method validation
topic	misc QH301-705.5 misc pharmacokinetics misc pharmacodynamics misc anticoagulant misc fucosylated glycosaminoglycan misc dHG-5 misc method validation misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc pharmacokinetics misc pharmacodynamics misc anticoagulant misc fucosylated glycosaminoglycan misc dHG-5 misc method validation misc Biology (General)
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title	Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from <i<Holothuria fuscopunctata</i<, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods
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title_sort	pharmacokinetics and pharmacodynamics of a depolymerized glycosaminoglycan from <i<holothuria fuscopunctata</i<, a novel anticoagulant candidate, in rats by bioanalytical methods
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title_auth	Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from <i<Holothuria fuscopunctata</i<, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods
abstract	dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber <i<Holothuria fuscopunctata</i<. 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 (<i<T<sub<max</sub<</i<) was at about 1 h, and the peak concentration (<i<C<sub<max</sub<</i<) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(<i<T<sub<1/2</sub<<sub<β</sub<</i<) 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.
abstractGer	dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber <i<Holothuria fuscopunctata</i<. 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 (<i<T<sub<max</sub<</i<) was at about 1 h, and the peak concentration (<i<C<sub<max</sub<</i<) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(<i<T<sub<1/2</sub<<sub<β</sub<</i<) 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.
abstract_unstemmed	dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber <i<Holothuria fuscopunctata</i<. 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 (<i<T<sub<max</sub<</i<) was at about 1 h, and the peak concentration (<i<C<sub<max</sub<</i<) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(<i<T<sub<1/2</sub<<sub<β</sub<</i<) 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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title_short	Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from <i<Holothuria fuscopunctata</i<, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods
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Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from <i<Holothuria fuscopunctata</i<, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods

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