利用微透析技术进行青藤碱治疗类风湿性关节炎药动-药效学考察  

Study on the pharmacokinetic-pharmacodynamic characteristics of sinomenine in rabbit's knee joint fluid by microdialysis

作　　者：邵继征[1] 田瑶[2] 周莉玲[2] 

机构地区：[1]广东食品药品职业学院,广东广州510520 [2]广州中医药大学,广东广州510006

出　　处：《中国医院药学杂志》2013年第19期1576-1580,共5页Chinese Journal of Hospital Pharmacy

基　　金：广东省自然科学基金(编号:10451052005005581);国家自然科学基金(编号:30672669)

摘　　要：目的:利用微透析技术建立类风湿性关节炎模型家兔关节腔局部青藤碱的PK-PD结合模型。方法:将微透析探针植入病理模型家兔关节腔中,给药后收集透析液,在同一份透析液中采用HPLC-MS测定药动学指标青藤碱,采用邻苯二甲醛柱前衍生HPLC-FLD测定精氨酸和瓜氨酸,并以精氨酸和瓜氨酸的抑制率为药效学指标,进行PK-PD结合研究。结果:药物效应与效应室浓度呈良好相关性,符合S型最大效应模型,并通过计算得出相应的PK-PD模型参数。结论:将微透析技术成功应用于关节腔局部的PK-PD结合模型研究中,并建立了家兔关节腔局部的青藤碱PK-PD结合模型,得到了药物效应、药物浓度及时间三者之间的关系。OBJECTIVE To establish the pharmacokinetic-pharmacodynamic （PK-PD） characteristics of sinomenine in rab bit＇s knee joint fluid by microdialysis. METHODS The microdialysis probes were implanted in rabbit＇s knee joint capsules, collecting the dialysates; the concentration of sinomenine in dialysate were detected by HPLC-MS, and arginine and citrulline in the same dialysate samples were detected by HPLC-FLD. The Sigmoid-Emax model was used to analyze the relationships among the drug concentration, time and effect. RESULTS The relationship between effect and drug concentration met the SigmoidEmx model and the model parameters were calculated. CONCLUSION Microdialysis can be used in the pharmacokinetic-phar- macodynamic（PK PD） characteristic study in rabbit＇s knee joint fluid and the PK-PD model of sinomenine; the relationships a mong effect and drug concentration and time were established successfully.

关 键 词：青藤碱 微透析 PK—PD结合模型 

分 类 号：R969.1[医药卫生—药理学]