葛根及复方中葛根素在大鼠体内的药动学研究

Pharmacokinetics of Puerarin in Pueraria and Its Compound Preparation in Rat

目的建立RP-HPLC测定大鼠血浆中葛根素浓度的方法,研究葛根提取物及复方脑得生片中葛根素的药动学特点,评价复方中其他配伍对葛根素药动学的影响。方法大鼠分别灌胃给予葛根提取物、复方脑得生片,断尾采血,离心,取血浆适量,加甲醇沉淀蛋白,取上清液过滤,用HPLC分析,以C18为固定相,流动相为甲醇-0.5%醋酸水溶液(25∶75),在250nm下检测,测定葛根素血药浓度,经3P97软件处理数据。结果葛根素血浆浓度在10～1000μg·L-1之间线性关系良好,最低检测浓度为6μg·L-1,高,中,低浓度样品回收率分别为89.9%,95.5%,89.7%。大鼠灌胃葛根提取物和脑得生片后的药-时曲线均符合二房室模型。灌胃脑得生片后,与灌胃葛根提取物相比,前者测定的葛根素ρmax和AUC0→∞分别比后者增加了2.23和3.03倍。结论本实验建立的RP-HPLC测定法专属、准确、灵敏,适用于葛根提取物及复方脑得生中葛根素的药动学研究。研究结果表明,脑得生片中的其他配伍药材可以促进葛根素的吸收,提高葛根素的生物利用度。

OBJECTIVE To develop a RP-HPLC method for the determination of the concentration ofpuerarin in rat plasma, to study the pharmacokinetics of pueraria extradite and Naodesheng tablet , and to investigate the effect of other components in compound on the pharmacokinetics of puerarin. METHODS The rats received 100 mg.kg^-1 pueraria extract and Naodesheng tablet by oral administration. After liquide extraction with methanol, plasma concentration of puerarin was measured. The pharmacokinetic parameters were calculated with 3P97 program. RESULTS A good linear relationship ofpuerarin was obtained in the range of 10 and 1 000 μg.L^-1, the lowest limit of determination was 6 μg.L^-1.The mean recoveries were 89.9%, 95.5%, 89.7% for high, middle, low concentrations of the samples respectively. The plasma concentration-time curves ofpuerarin were fitted with two-compartments model. The AUC0→∞ and Pmax of puerarin were increased in the Naodesheng group, compared with 100 mg.kg^-1 pueraria extract group. CONCLUSION The HPLC method was selective, accurate and sensitive. The results indicated that the other herbs improved the absorption of puerarin and increased the bioavailability of puerarin significantly.