金森脑泰注射剂中葛根素在正常和缺血再灌模型大鼠体内的药动学研究

目的　探讨脑血管新药金森脑泰注射剂 (商品名 )中葛根素在正常和缺血再灌大鼠体内的动力学过程。方法　对正常大鼠及缺血再灌大鼠静脉注射金森脑泰注射液后不同时间采血 ,用HPLC PAD(二极管阵列紫外检测器 )测定葛根素血药浓度。 3P87软件拟合药动学参数。结果　静注金森脑泰后葛根素在正常大鼠体内呈一室模型 ,t1/ 2α为 18min ,在脑缺血再灌大鼠体内呈二室模型分布 ,t1/ 2α和t1/ 2 β分别是 7.7和 38.4min。平均驻留时间 (MRT)和清除率 (CLtot)分别为 2 4.0 ,43.9min和0 .0 14,0 .0 0 3L·min-1·kg-1。后者特征HPLC图谱经PAD分析 ,3个未知成分的色谱峰中有两个与葛根素的紫外光谱 (2 0 0～ 80 0nm)相似 ,它们的峰面积的经时消长过程与葛根素色谱峰的峰面积的经时消长变化相似 ,相关系数分别为 0 .995 7,0 .9990。结论　利用未知成分的峰面积消长变化 ,求得相对药动学参数 ,有助于更全面地反映中药复方 (有效部位 )的药物代谢规律。同时也提示我们 ,作为葛根黄酮的主要有效成分的葛根素的药动学参数可以基本反映葛根黄酮的药动学参数。

Pharmacokinetics of puerarin in normal and cerebral ischemia reperfusion rats

OBJECTIVE To study the pharmacokinetics of puerarin,an active component in natural cerebral nutrition(CBN),in normal and cerebral ischemia reperfusion rats.METHODS The blood samples at different times after administration were collected.The plasma concentrations of puerarin were determined by HPLC-PAD(photodiode-array detector).The pharmacokinetic parameters were accessed by 3P87.RESULTS Puerarin was disposed as one-compartment model in normal rats,while as tow-compartment model in cerebral ischemia reperfusion rats,which accompanied with three unknown chromatography peaks under the puerarin's fluid phase condition.The three peaks were analyzed by PAD and two of them had similar spectrum as puerarin over the range of 200 nm to 800 nm.These two peaks' area flow and declined as the way of puerarin.Their correlative coefficients were 0.995 7 and 0.999 0,respectively.CONCLUSION Puerarin's clearance in normal rats was greatly faster than that in cerebral ischemia reperfusion rats.The metabolism of active components is necessary to consider under pathologic condition as an effective ingredient of pueraria isoflavanoids,puerarin may be related to its pharmacokinetics.