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An integrated pharmacokinetic study of Dengzhanxixin injection in rats by combination of multicomponent pharmacokinetics and anti-myocardial ischemic assay

This study aimed to investigate the integrated pharmacokinetics (PK) of Dengzhanxixin injection (EBI) in rats by combination of multicomponent PK and pharmacological assays. First, the protective effects of 13 main components (30 mg kg(−1) per day, i.v. for 7 days) on isoprenaline-induced myocardial...

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Autores principales: Huang, Jianyong, Su, Ya, Yang, Chunlei, Li, Shaoguang, Wu, Youjia, Chen, Bing, Lin, Xinhua, Huang, Liying, Yao, Hong, Shi, Peiying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070076/
https://www.ncbi.nlm.nih.gov/pubmed/35530075
http://dx.doi.org/10.1039/c9ra03917a
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author Huang, Jianyong
Su, Ya
Yang, Chunlei
Li, Shaoguang
Wu, Youjia
Chen, Bing
Lin, Xinhua
Huang, Liying
Yao, Hong
Shi, Peiying
author_facet Huang, Jianyong
Su, Ya
Yang, Chunlei
Li, Shaoguang
Wu, Youjia
Chen, Bing
Lin, Xinhua
Huang, Liying
Yao, Hong
Shi, Peiying
author_sort Huang, Jianyong
collection PubMed
description This study aimed to investigate the integrated pharmacokinetics (PK) of Dengzhanxixin injection (EBI) in rats by combination of multicomponent PK and pharmacological assays. First, the protective effects of 13 main components (30 mg kg(−1) per day, i.v. for 7 days) on isoprenaline-induced myocardial infarction (MI) in mice were evaluated by measuring electrocardiogram and serum creatine kinase (CK) activity, and observing cardiac pathological changes. Second, the quantitative analysis method of the main components in rat plasma was established and applied to pharmacokinetic study of EBI in rats (0.72 mL kg(−1) and 3.2 mL kg(−1) of 10 times concentrated EBI, single i.v.). Third, based on the multicomponent PK and anti-MI effects, PK markers were selected, and the integrated PK of EBI in rats were investigated using “plasma drug concentration sum method” and “AUC weighting integrated method”. In the in vivo anti-MI study, the ST segment elevation seldom occurred and the serum CK significantly decreased (P < 0.05 vs. model group); additionally tissue sections showed mild edema and inflammatory infiltration, and there was a little loss of striations in heart tissue in scutellarin, 3-caffeoylquinic acid (3-CQA), apigenin-7-O-glucuronide (A-7-O-G) and 4,5-dicaffeoylquinic acid (4,5-diCQA) treated groups, suggesting that scutellarin, 3-CQA, A-7-O-G and 4,5-diCQA were the main anti-MI effective substances. In the PK study, the systematic exposure level of scutellarin, erigoster B, 3,4-diCDOA (or 4,9-diCDOA), A-7-O-G, and 4,5-diCQA is relatively high. Considering the contents in EBI, anti-MI efficacy and PK properties of each component, scutellarin, 3-CQA, A-7-O-G, erigoster B, 3,4-diCDOA (or 4,9-diCDOA) and 4,5-diCQA were selected as pharmacokinetic markers to characterize the integrated pharmacokinetic behavior of EBI in vivo. The integrated pharmacokinetic study of EBI in rats could reveal the overall in vivo process and improve the safety and rationality of the clinical use of EBI.
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spelling pubmed-90700762022-05-05 An integrated pharmacokinetic study of Dengzhanxixin injection in rats by combination of multicomponent pharmacokinetics and anti-myocardial ischemic assay Huang, Jianyong Su, Ya Yang, Chunlei Li, Shaoguang Wu, Youjia Chen, Bing Lin, Xinhua Huang, Liying Yao, Hong Shi, Peiying RSC Adv Chemistry This study aimed to investigate the integrated pharmacokinetics (PK) of Dengzhanxixin injection (EBI) in rats by combination of multicomponent PK and pharmacological assays. First, the protective effects of 13 main components (30 mg kg(−1) per day, i.v. for 7 days) on isoprenaline-induced myocardial infarction (MI) in mice were evaluated by measuring electrocardiogram and serum creatine kinase (CK) activity, and observing cardiac pathological changes. Second, the quantitative analysis method of the main components in rat plasma was established and applied to pharmacokinetic study of EBI in rats (0.72 mL kg(−1) and 3.2 mL kg(−1) of 10 times concentrated EBI, single i.v.). Third, based on the multicomponent PK and anti-MI effects, PK markers were selected, and the integrated PK of EBI in rats were investigated using “plasma drug concentration sum method” and “AUC weighting integrated method”. In the in vivo anti-MI study, the ST segment elevation seldom occurred and the serum CK significantly decreased (P < 0.05 vs. model group); additionally tissue sections showed mild edema and inflammatory infiltration, and there was a little loss of striations in heart tissue in scutellarin, 3-caffeoylquinic acid (3-CQA), apigenin-7-O-glucuronide (A-7-O-G) and 4,5-dicaffeoylquinic acid (4,5-diCQA) treated groups, suggesting that scutellarin, 3-CQA, A-7-O-G and 4,5-diCQA were the main anti-MI effective substances. In the PK study, the systematic exposure level of scutellarin, erigoster B, 3,4-diCDOA (or 4,9-diCDOA), A-7-O-G, and 4,5-diCQA is relatively high. Considering the contents in EBI, anti-MI efficacy and PK properties of each component, scutellarin, 3-CQA, A-7-O-G, erigoster B, 3,4-diCDOA (or 4,9-diCDOA) and 4,5-diCQA were selected as pharmacokinetic markers to characterize the integrated pharmacokinetic behavior of EBI in vivo. The integrated pharmacokinetic study of EBI in rats could reveal the overall in vivo process and improve the safety and rationality of the clinical use of EBI. The Royal Society of Chemistry 2019-08-13 /pmc/articles/PMC9070076/ /pubmed/35530075 http://dx.doi.org/10.1039/c9ra03917a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Huang, Jianyong
Su, Ya
Yang, Chunlei
Li, Shaoguang
Wu, Youjia
Chen, Bing
Lin, Xinhua
Huang, Liying
Yao, Hong
Shi, Peiying
An integrated pharmacokinetic study of Dengzhanxixin injection in rats by combination of multicomponent pharmacokinetics and anti-myocardial ischemic assay
title An integrated pharmacokinetic study of Dengzhanxixin injection in rats by combination of multicomponent pharmacokinetics and anti-myocardial ischemic assay
title_full An integrated pharmacokinetic study of Dengzhanxixin injection in rats by combination of multicomponent pharmacokinetics and anti-myocardial ischemic assay
title_fullStr An integrated pharmacokinetic study of Dengzhanxixin injection in rats by combination of multicomponent pharmacokinetics and anti-myocardial ischemic assay
title_full_unstemmed An integrated pharmacokinetic study of Dengzhanxixin injection in rats by combination of multicomponent pharmacokinetics and anti-myocardial ischemic assay
title_short An integrated pharmacokinetic study of Dengzhanxixin injection in rats by combination of multicomponent pharmacokinetics and anti-myocardial ischemic assay
title_sort integrated pharmacokinetic study of dengzhanxixin injection in rats by combination of multicomponent pharmacokinetics and anti-myocardial ischemic assay
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070076/
https://www.ncbi.nlm.nih.gov/pubmed/35530075
http://dx.doi.org/10.1039/c9ra03917a
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