Establishment of PK-PD Binding Model for Multi-Components of Crossbow Medicine Microemulsion Based on a Rat Model of Knee Osteoarthritis
10.14148/j.issn.1672-0482.2025.0804
- VernacularTitle:基于膝骨性关节炎大鼠模型弩药微乳多成分PK-PD结合模型的建立
- Author:
Chan ZHAO
1
;
Huan XIE
;
Jian XU
;
Yao LIU
;
Fangfang YANG
;
Yinglong CHEN
;
Yongping ZHANG
Author Information
1. 贵州中医药大学药学院,贵州 贵阳 550025
- Publication Type:Journal Article
- Keywords:
crossbow medicine microemulsion multi-components;
knee osteoarthritis;
UPLC;
pharmacokinetics-pharmacodynam-ics
- From:
Journal of Nanjing University of Traditional Chinese Medicine
2025;41(6):804-812
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.
