银杏酮酯及其HP-β-环糊精包合物在大鼠体内的药物动力学  

Pharmacokinetics of GBE50 and its HP-β-cyclodextrin complex in rats

作　　者：赵建彬[1] 卢文芬[1] 陈水钫[1] 漆林艳[1] 陈建海[1] 

机构地区：[1]南方医科大学南方医院药学部,广州510515

出　　处：《中南药学》2011年第6期433-436,共4页Central South Pharmacy

摘　　要：目的建立测定大鼠血浆中槲皮素、山柰素浓度的反相高效液相色谱法,研究银杏酮酯颗粒及其HP-β-环糊精包合物大鼠灌胃后体内药物动力学行为。方法血浆标本水解后,经乙酸乙酯提取,以甲醇-水-磷酸为流动相;12只大鼠随机均分为2组,分别灌胃银杏铜酯颗粒及其包合物后,检测血浆药物浓度。药时曲线采用DAS药代计算程序处理。结果槲皮素在2.6~264.0μg.mL-1,山柰素在1.2~120μg.mL-1与峰面积线性关系良好。结果表明GBE50经包合后,槲皮素主要药动学参数Cmax,tmax,AUC0-t,AUC0-∞分别为（0.219 4±0.034 5）mg.L-1、（4±1）h、（0.872±0.243）h.mg.L-1、（0.843±0.431）h.mg.L-1;参比制剂中槲皮素主要药动学参数Cmax、tmax、AUC0-t、AUC0-∞分别为（0.164 6±0.004 1）mg.L-1、（8±3）h、（0.434±0.132）h.mg.L-1、（0.577±0.143）h.mg.L-1。GBE50经包合后山柰素主要药动学参数Cmax、tmax、AUC0-t、AUC0-∞分别为（0.016 3±0.003）mg.L-1、（1±0.2）h、（0.077±0.023）h.mg.L-1、（0.09±0.04）h.mg.L-1;参比制剂中山柰素主要药动学参数Cmax、tmax、AUC0-t、AUC0-∞分别为（0.015 5±0.002）mg.L-1、（8±3）h、（0.023±0.003 5）h.mg.L-1、（0.026±0.011 2）h.mg.L-1.以槲皮素计,包合物的相对生物利用度为146.10%;以山柰素计,包合物的相对生物利用度为346.15%。结论该法准确,适用于槲皮素和山柰素血浆浓度的测定;制备的银杏酮酯-羟丙基-β-环糊精包合物与银杏铜酯颗粒相比,吸收明显增加。Objective To establish an RP-HPLC method for the determination of quercetin and kaempferol concentration and study the pharmacokinetic behaviors of quercetin and kaempferol in rats after administration of GBE50 and its complex（GBE50-HP-β-CD）.Methods Drug in the plasma was extracted and determined by HPLC.The mobile phase was composed of methanol-water-orthophosphoric acid.Twelve rats randomized into 2 groups were given GBE50 and its complex respectively.The pharmacokinetic parameters were calculated by DAS software.Results The concentration-time data of GBE50 after the oral administration best fit the one-compartment model.The main pharmacokinetic parameters of quercetin were as follows： the Cmax,tmax,AUC0-t,AUC0-∞ of the test sample was（0.219 4±0.034 5）mg·L-1-1,（4±1）h,（0.872±0.243）h·mg·L-1,and（0.843±0.431） h·mg·L-1;that of the reference was（0.164 6±0.004 1）mg·L-1,（8±3）h,（0.434±0.132） h·mg·L-1,and（0.577±0.143）h·mg·L-1.The main pharmacokinetic parameters of kaempferol were as follows： the Cmax,tmax,AUC0-t,AUC0-∞ of the test sample was（0.016 3±0.003）mg·L-1,（1±0.2）h,（0.077±0.023）h·mg·L-1,（0.09±0.04） h·mg·L-1;that of the reference was（0.015 5±0.002）mg·L-1,（8±3）h,（0.023±0.003 5） h·mg·L-1,and（0.026±0.011 2）h·mg·L-1.Conclusion The method is suitable for the determination of quercetin and kaempferol plasma concentration in rats.Absorption in GBE50-HP-β-CD complex has increased compared with that of GBE50.

关 键 词：银杏酮酯 包合物 槲皮素 山柰素 药动学 

分 类 号：R969.1[医药卫生—药理学] R927.1[医药卫生—药学]