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A pharmacokinetics–pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats

CONTEXT: Total Glucosides of Paeony (TGP) capsule possesses various hepatoprotective activities. No study is available concerning TGP’s concentration–effect relationship on hepatoprotection. OBJECTIVE: To establish a pharmacokinetics–pharmacodynamics (PK-PD) modelling on TGP capsule’s hepatoprotecti...

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Autores principales: Jiang, Ninghua, Zheng, Bohong, Feng, Yihan, Yin, Lei, Liu, Yuanrong, Cao, Lujing, Zheng, Ning, Wu, Suxiang, Ding, Baoyue, Huang, Xuan, Wang, Jeffrey, Zhan, Shuyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218697/
https://www.ncbi.nlm.nih.gov/pubmed/34152236
http://dx.doi.org/10.1080/13880209.2021.1937232
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author Jiang, Ninghua
Zheng, Bohong
Feng, Yihan
Yin, Lei
Liu, Yuanrong
Cao, Lujing
Zheng, Ning
Wu, Suxiang
Ding, Baoyue
Huang, Xuan
Wang, Jeffrey
Zhan, Shuyu
author_facet Jiang, Ninghua
Zheng, Bohong
Feng, Yihan
Yin, Lei
Liu, Yuanrong
Cao, Lujing
Zheng, Ning
Wu, Suxiang
Ding, Baoyue
Huang, Xuan
Wang, Jeffrey
Zhan, Shuyu
author_sort Jiang, Ninghua
collection PubMed
description CONTEXT: Total Glucosides of Paeony (TGP) capsule possesses various hepatoprotective activities. No study is available concerning TGP’s concentration–effect relationship on hepatoprotection. OBJECTIVE: To establish a pharmacokinetics–pharmacodynamics (PK-PD) modelling on TGP capsule’s hepatoprotection after a single oral administration in hepatic injury rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into five groups (n = 6): control, model (hepatic injury), treated-H (2.82 g/kg), treated-M (1.41 g/kg), and treated-L (0.705 g/kg) groups. All treated groups rats were intragastrically administered a single dose. An LC-MS/MS method was applied to determine paeoniflorin (Pae) and albiflorin (Alb) in rat serum. The effects of single-dose TGP on serum alanine transaminase (ALT), aspartate transaminase (AST) and total bile acid (TBA) were evaluated in hepatic injury rats. RESULTS: Single dose (2.82, 1.41, or 0.705 g/kg) TGP capsule could real-time down-regulate serum TBA but not ALT and AST in hepatic injury rats within 20 h. An inhibitory effect Sigmoid E(max) of PK-PD modelling was established using Pae and Alb as PK markers and serum TBA as effect index. Pharmacodynamic parameters were calculated. For treated-H, treated-M and treated-L group, respectively, E(0) were 158.1, 226.9 and 245.4 μmol/L for Pae, 146.1, 92.9 and 138.4 μmol/L for Alb, E(max) were 53.0, 66.0, and 97.1 μmol/L for Pae, 117.4, 249.7 and 60.0 μmol/L for Alb, and EC(50) were 9.3, 5.2 and 2.7 μg/mL for Pae, 2.3, 0.8, and 0.8 μg/mL for Alb. DISCUSSION AND CONCLUSIONS: Serum TBA is a sensitive effect index for TGP’s single dose PK-PD modelling, and it is potential for further multi-dose studies of TGP’ effect on hepatic injury. The study provides valuable information for TGP’s mechanistic research and rational clinical application.
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spelling pubmed-82186972021-06-30 A pharmacokinetics–pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats Jiang, Ninghua Zheng, Bohong Feng, Yihan Yin, Lei Liu, Yuanrong Cao, Lujing Zheng, Ning Wu, Suxiang Ding, Baoyue Huang, Xuan Wang, Jeffrey Zhan, Shuyu Pharm Biol Short Communication CONTEXT: Total Glucosides of Paeony (TGP) capsule possesses various hepatoprotective activities. No study is available concerning TGP’s concentration–effect relationship on hepatoprotection. OBJECTIVE: To establish a pharmacokinetics–pharmacodynamics (PK-PD) modelling on TGP capsule’s hepatoprotection after a single oral administration in hepatic injury rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into five groups (n = 6): control, model (hepatic injury), treated-H (2.82 g/kg), treated-M (1.41 g/kg), and treated-L (0.705 g/kg) groups. All treated groups rats were intragastrically administered a single dose. An LC-MS/MS method was applied to determine paeoniflorin (Pae) and albiflorin (Alb) in rat serum. The effects of single-dose TGP on serum alanine transaminase (ALT), aspartate transaminase (AST) and total bile acid (TBA) were evaluated in hepatic injury rats. RESULTS: Single dose (2.82, 1.41, or 0.705 g/kg) TGP capsule could real-time down-regulate serum TBA but not ALT and AST in hepatic injury rats within 20 h. An inhibitory effect Sigmoid E(max) of PK-PD modelling was established using Pae and Alb as PK markers and serum TBA as effect index. Pharmacodynamic parameters were calculated. For treated-H, treated-M and treated-L group, respectively, E(0) were 158.1, 226.9 and 245.4 μmol/L for Pae, 146.1, 92.9 and 138.4 μmol/L for Alb, E(max) were 53.0, 66.0, and 97.1 μmol/L for Pae, 117.4, 249.7 and 60.0 μmol/L for Alb, and EC(50) were 9.3, 5.2 and 2.7 μg/mL for Pae, 2.3, 0.8, and 0.8 μg/mL for Alb. DISCUSSION AND CONCLUSIONS: Serum TBA is a sensitive effect index for TGP’s single dose PK-PD modelling, and it is potential for further multi-dose studies of TGP’ effect on hepatic injury. The study provides valuable information for TGP’s mechanistic research and rational clinical application. Taylor & Francis 2021-06-21 /pmc/articles/PMC8218697/ /pubmed/34152236 http://dx.doi.org/10.1080/13880209.2021.1937232 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Jiang, Ninghua
Zheng, Bohong
Feng, Yihan
Yin, Lei
Liu, Yuanrong
Cao, Lujing
Zheng, Ning
Wu, Suxiang
Ding, Baoyue
Huang, Xuan
Wang, Jeffrey
Zhan, Shuyu
A pharmacokinetics–pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats
title A pharmacokinetics–pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats
title_full A pharmacokinetics–pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats
title_fullStr A pharmacokinetics–pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats
title_full_unstemmed A pharmacokinetics–pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats
title_short A pharmacokinetics–pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats
title_sort pharmacokinetics–pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218697/
https://www.ncbi.nlm.nih.gov/pubmed/34152236
http://dx.doi.org/10.1080/13880209.2021.1937232
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