南京中医药大学学报2025，Vol.41Issue(6)：804-812,9.DOI:10.14148/j.issn.1672-0482.2025.0804
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
Establishment of PK-PD Binding Model for Multi-Components of Crossbow Medicine Microemulsion Based on a Rat Model of Knee Osteoarthritis
摘要
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.关键词
弩药微乳多成分/膝骨性关节炎/UPLC/药动学-药效学Key words
crossbow medicine microemulsion multi-components/knee osteoarthritis/UPLC/pharmacokinetics-pharmacodynam-ics分类
医药卫生引用本文复制引用
赵婵,谢欢,徐剑,刘耀,杨芳芳,陈迎龙,张永萍..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[J].南京中医药大学学报,2025,41(6):804-812,9.基金项目
国家自然科学基金面上项目(82160753) （82160753）
贵州省高层次创新型人才项目(黔科合平台人才-GCC[2023]037) （黔科合平台人才-GCC[2023]037）
国家苗药工程技术研究中心能力提升项目(黔科合中引地[2023]006) （黔科合中引地[2023]006）
贵州省高等学校中药民族药(苗药)新剂型新制剂工程研究中心(黔教技[2022]022) （苗药）
