A pharmacokinetics–pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats
2021
Jiang, Ninghua | Zheng, Bohong | Feng, Yihan | Yin, Lei | Liu, Yuanrong | Cao, Lujing | Zheng, Ning | Wu, Suxiang | Ding, Baoyue | Huang, Xuan | Wang, Jeffrey | Zhan, Shuyu
Total Glucosides of Paeony (TGP) capsule possesses various hepatoprotective activities. No study is available concerning TGP’s concentration–effect relationship on hepatoprotection. To establish a pharmacokinetics–pharmacodynamics (PK-PD) modelling on TGP capsule’s hepatoprotection after a single oral administration in hepatic injury rats. 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. 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, E₀ were 158.1, 226.9 and 245.4 μmol/L for Pae, 146.1, 92.9 and 138.4 μmol/L for Alb, Eₘₐₓ were 53.0, 66.0, and 97.1 μmol/L for Pae, 117.4, 249.7 and 60.0 μmol/L for Alb, and EC₅₀ were 9.3, 5.2 and 2.7 μg/mL for Pae, 2.3, 0.8, and 0.8 μg/mL for Alb. 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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