萸连巴布膏中盐酸巴马汀和小檗碱的药动学研究

目的:建立家兔血浆中巴马汀和小檗碱HPLC测定方法,测定萸连巴布剂经皮给予后巴马汀和小檗碱的血药浓度,计算药代动力学参数。方法:家兔按12 g.kg-1生药经皮给药,HPLC测定不同时间点血浆中巴马汀和小檗碱的浓度,并计算主要药动学参数。结果:血浆中巴马汀和小檗碱73.75～1 180 ng.mL-1线性关系良好(r≥0.999),平均回收率分别为82.95%,85.35%,日内和日间差异RSD均小于15%。家兔透皮给萸连巴布剂后巴马汀和小檗碱的药-时曲线呈一室模型,巴马汀和小檗碱的主要药动学参数分别为:Cmax(74.208±32.890),(541.869±367.341)ng.mL-1;Tmax(3.3164±2.490),(2.911±2.259)h;AUC(0～t)(1 259.118±720.882),(9 847.251±7 145.931)ng.mL-1.h;MRT(0～t)(13.492±1.833),(14.779±2.430)h;t1/2(6.842±2.225),(9.913±6.820)h。结论:本实验方法简便、可靠,可用于巴马汀和小檗碱血药浓度分析及其药代动力学研究;萸连巴布剂经皮吸收迅速,释放缓慢,长时间给药可以维持较高的血药浓度,发挥长效作用。

Pharmacokinetics of Palmatine and Berberine of Yulian Cataplasm

Objective: To establish a sensitive and specific HPLC method for determination of the plasma concentration of palmatine and berberine in rabbit plasma and study pharmacokinetic parameters. Method: Rabbits were given Yulian cataplasm 12 g ·kg^-1 by transdermal administration.Then detected the plasma concentration of palmatine and berberine at different time points by HPLC and estimated major pharmacokinetic parameters. Result: The calibration curve of palmatine and berberine was linear over the range from 73.75 ng ·mL^-1 to 1 180 ng ·mL^-1 with a correlation coefficient of 0.999.The mean recovery rate of palmatine was 82.95% and berberine's was 85.35%.The RSD within day and between days were less than 15%.The concentration-time curves of palmatine or berberine conformed to a one compartment model.The main pharmaeokinetic parameters of palmatine or berberine were estimated to be as follows:C_max(74.208±32.890),(541.869±367.341)ng ·mL^-1;T_max (3.3164±2.490),(2.911±2.259)h ;AUC_(0~t) (1 259.118±720.882),(9 847.251±7 145.931)ng ·mL^-1 ·h^-1; MRT_(0~t)(13.492±1.833),(14.779±2.430)h; t_1/2(6.842±2.225),(9.913±6.820)h. Conclusion: The established HPLC method is simple and sensitive to determine the concentration of palmatine or berberine in rabbit plasma and can be used for pharmacokinetic studies.From the result of the tests,we can find that palmatine or berberine were quickly absorded,and slowly released.So Yulian cataplasm can exert long-term effects.