海南医科大学学报2025，Vol.31Issue(20)：1535-1540,6.DOI:10.13210/j.cnki.jhmu.20241127.002
高血浆蛋白结合率药物对千金藤素血浆蛋白结合率的影响
Effects of drugs with high plasma protein binding rate on plasma protein binding rate of cepharanthine
摘要
Abstract
Objective:To investigate the impact of drugs with high plasma protein binding rate on the plasma protein binding rate of cepharanthine.Methods:The molecular docking method was employed to investigate the binding interactions between ceph-aranthine and plasma proteins.Discovery Studio 2021 was utilized to screen for drugs that compete with cepharanthine within a mo-lecular drug library.A method was established for the determination of cepharanthine in dog plasma and dialysis fluid.Plasma sam-ples and phosphate buffer solution samples underwent liquid-liquid extraction and were analyzed using liquid chromatography-tandem mass spectrometry.The effects of riociguat,delamanid,montelukast,and racambrisentan on the plasma protein binding rate of cepharanthine were assessed through equilibrium dialysis.Results:Through molecular docking,candidate drugs with high plasma protein binding that have the same binding site as cepharanthine were screened from the marketed drug molecule library.These drugs may compete with cepharanthine for binding to plasma proteins.A total of 4 drugs,riociguat,delamanid,montelukast,and racambrisentan,were selected for in vitro competitive binding experiments.The results showed that the protein binding rate of cepharanthine to dog plasma was very high,reaching(99.47±0.13)%.Combining riociguat,montelukast,and racambrisentan had no significant effect on the plasma protein binding of cepharanthine at the concentrations tested.Combining low-concentration delamanid(200 ng/mL)also had no significant effect on the plasma protein binding rate of cepharanthine,while combining high-concentration delamanid(500 ng/mL)significantly increased the concentration of free cepharanthine in plasma.Conclusion:Rio-ciguat,montelukast,and ambrisentan do not have any obvious competitive relationship with cepharanthine,but delamanid can re-duce the plasma protein binding rate of cepharanthine.关键词
血浆蛋白结合率/竞争性/药物相互作用/千金藤素/联合用药/药物代谢动力学Key words
Plasma protein binding rate/Competitive/Drug interaction/Cepharanthine/Combined medication/Pharmaco-kinetics分类
药学引用本文复制引用
苑硕,冯君豪,董静,龚伟,高春生..高血浆蛋白结合率药物对千金藤素血浆蛋白结合率的影响[J].海南医科大学学报,2025,31(20):1535-1540,6.基金项目
This study was supported by the National Science and Technology Major Projects for"Major New Drugs Innovation and Development"(2018ZX09711003-008-001)国家科技重大专项"重大新药创制"项目(2018ZX09711003-008-001) （2018ZX09711003-008-001）
