血液微透析技术分析阿魏酸口服给药后药代动力学过程

Pharmacokinetics Analysis of Ferulic Acid after Oral Administration in Rats by Blood Microdialysis Technique

目的:应用血液微透析技术测定阿魏酸口服给药后药代动力学参数。方法:采用浓差法(增量法和减量法)考察探针回收率的日内稳定性及灌流速度、阿魏酸质量浓度、温度对探针回收率的影响,通过零净流量法测定阿魏酸体外回收率,并将结果与浓差法所测回收率进行比较。采用血液微透析法进行体内药动学研究,HPLC测定透析液中阿魏酸含量。结果:探针回收率日内稳定性良好;体外回收率与阿魏酸质量浓度无关,与灌流速度成指数型负相关;温度越高,回收率越高;利用零净通量法能准确地测定透析介质中阿魏酸含量及回收率;增量法、减量法及零净通量法测定的回收率一致。在2.5μL.min-1流速下,体内平均回收率(28.69±1.95)%,口服给药后阿魏酸9.33 min达峰值,消除半衰期12.52 min。结论:微透析取样技术可用于阿魏酸的药动学研究,减量法可作为体内微透析研究中阿魏酸回收率的测定方法。

Objective：To determine pharmacokinetic parameters of ferulic acid after oral administration by blood microdialysis technique.Method：Days stability of probe recovery and effects of perfusion rate,the concentration of ferulic acid,temperature on probe recovery were investigated by concentration difference method（incremental and reduction method）;Zero-net flux method was adopted to determine in vitro recovery of ferulic acid,result of this method was compared with concentration difference method.In vivo pharmacokinetic study was applied by blood microdialysis method,the content of ferulic acid was determined by HPLC.Result：Days stability of probe recovery was good;In vitro recovery had no correlation with the concentration of ferulic acid,but presented exponential negative correlation with perfusion rate and positive correlation with temperature;The content of ferulic acid and recovery in dialysis medium could be accurately determined by zero-net flux method.Recovery of incremental method,reduction method and zero-net flux method was the same.In vivo average recovery was（28.69 ±1.95） % with flow rate of 2.5 μL.min-1,Cmax of ferulic acid was reached at 9.33 min and t1 /2β was 12.52 min after oral administration.Conclusion：Microdialysis sampling technique could be used for pharmacokinetic study of ferulic acid and reduction method could be used to determine recovery of ferulic acid in in vivo microdialysis study.