泻心汤黄酮类成分在大鼠体内的药代动力学研究  

Pharmacokinetics of flavonoids from Xiexin decoction in rats

作　　者：闫晶超[1] 刘兆明[1] 王天明[1] 石荣[1] 马越鸣[1] 

机构地区：[1]上海中医药大学中药药代动力学实验室,上海201203

出　　处：《药学学报》2007年第7期722-729,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(90409008);上海市科委基金资助项目(04DZ19844);上海市重点学科建设项目资助(T0301)

摘　　要：研究泻心汤中黄酮类成分在大鼠体内药代动力学规律。大鼠灌胃给予泻心汤12g·kg^-1，给药前及给药后不同时间采集血样或尿样，HPLC法测定黄酮类成分浓度，血药浓度-时间数据和尿药排泄量-时间数据用DAS软件进行动力学分析。采用大鼠肾匀浆温孵法，进行黄芩苷的体外代谢研究。结果显示，黄芩苷、汉黄芩苷血药浓度迅速达峰，药时曲线呈现双峰现象，消除T1/2均为6h左右；黄芩苷、汉黄芩苷、黄芩素、汉黄芩素在尿中均有排泄，尿中排泄量占给药量均〈10%，尿排泄T1/2在6-8h；大鼠肾匀浆可将黄芩苷代谢生成黄芩素，酶动力学参数Vmax=702nmol·min^-1·g^-1（protein），Km=135μmol·L^-1。可见，泻心汤中黄酮类成分可迅速吸收进入体内；黄芩苷、汉黄芩苷、黄芩素、汉黄芩素均可从尿排泄，但尿药排泄量较少；肾脏可将黄芩苷代谢成黄芩素。To study the pharmacokinetics of flavonoids from Xiexin decoction in rats. SD rats were given a single ig dose of Xiexin decoction 12 g · kg^-1, plasma and urine were collected before and after dosing. Flavonoids components in plasma and urine were measured by HPLC. Pharmacokinetic parameters were determined from the plasma concentration-time data and urinary excretion-time data with the DAS software package. Baicalin was incubated with the rat renal homogenate to investigate its metabolism in vitro. After oral administration of Xiexin decoction baicalin and wogonoside were quickly absorbed and exhibited double peak phenomena in their plasma concentrations. The first peaks in plasma concentrations of baicalin and wogonoside reached Cmax1 of （ 10 ± 8） and （ 1.5 ± 0.5 ） mg · L^- 1 at Tmax1 of （0.27 ± 0. 09） and （0. 17 ±0. 00） h, while the second peaks reached Cmax2 of （3. 9 ±0. 5） and （0. 74 ±0. 11） mg · L^-1 at Tmax2 of （7. 6 ± 2.6） and （ 16.0 ± 0.0） h, respectively. The T1/2 of baicalin and wogonoside were （7±3） and （6.4 ±2. 1） h, AUC0-∞ were （57 ± 12） and （15 ±3） mg ·h · L^-1, respectively. After oral administration of Xiexin decoction, not only baicalin and wogonoside but also baicalein and wogonin can be detected in the urine. The amounts of baicalin, wogonoside, baicalein and wogonin excreted from urine during0-72 h were （1.4±0.3）, （3.4±1.3）, （2.2±0.97）, （10 ±4） % of dose given in rats, respectively. The excretion T1/2 of the four flavonoids were （6.9 ± 2. 1 ）, （9 ± 4）, （8.2 ± 2.0） and （7.2 ± 1.8） h, respectively. Baicalin was metabolized into baicalein in the rat renal homogenate in vitro, and the kinetic parameters were measured as Vmax = 702 nmol · min^-1· g^-1 （protein） and Km = 135 μmol · L^-1. After oral administration of Xiexin decoction, flavonoids can be absorbed quickly. Only a small quantity of baicalin, wogonoside, baicalein and wogonin were excreted from urine. Baicalin may be metabo

关 键 词：黄酮类 泻心汤 药代动力学 高效液相色谱法 

分 类 号：R917[医药卫生—药物分析学] R969.1[医药卫生—药学]