论文部分内容阅读
目的:研究延胡索乙素(THP)灌胃给药在清醒大鼠脑局部的药动学特性。方法:采用微透析采样技术,以清醒大鼠为实验模型,连续收集给药(40 mg·kg~(-1))后大鼠脑纹状体透析液,高效液相色谱(HPLC)法测定THP浓度,经回收率校正后,用PK Solver 2.0药动学软件按非房室模型计算主要药动学参数。结果:THP在清醒大鼠脑局部的药动学参数t1/2为(2.0±0.46)h;tmax为(1.18±0.19)h;Cmax为(4 090.73±151.45)ng·mL~(-1);AUC0-inf为(15.05±1.02)ng·mL~(-1)·h~(-1);MRT0-inf为(3.72±0.21)h。结论:所采用的微透析技术能实现活体连续取样,所建立的HPLC分析方法经方法学考察表明该方法精密度、准确度高,重现性好;微透析-HPLC法适用于延胡索乙素在大鼠脑局部的药动学研究,为其脑部靶向制剂的开发与临床应用提供实验依据。
Objective: To study the pharmacokinetics of tetrahydropalmatine (THP) administered intragastrically in awake rats. Methods: The rat model of striatum was collected continuously (40 mg · kg ~ (-1)) with dialysis technique and sober rat model, and the content of total cholesterol in striatum was determined by high performance liquid chromatography THP concentration, corrected for recovery, the main pharmacokinetic parameters were calculated on a non-compartmental model using PK Solver 2.0 pharmacokinetic software. Results: The pharmacokinetic parameters of THP in awake rats were (2.0 ± 0.46) h, tmax = (1.18 ± 0.19) h, Cmax = (9090.73 ± 151.45) ng · mL -1 ; AUC0-inf was (15.05 ± 1.02) ng · mL -1 · h -1; MRT0-inf was (3.72 ± 0.21) h. CONCLUSION: The microdialysis technique used in this study can achieve continuous sampling in vivo. The HPLC analysis method established by the method showed that the method has high precision, high accuracy and good reproducibility. The microdialysis-HPLC method is suitable for the determination of tetrahydropalmatine Local pharmacokinetics of rat brain provides experimental evidence for the development and clinical application of its targeted preparation in the brain.