Li Pengyue, Zhong Linying, Yang Linjie, Bai Jie, Lu Yang, Du Shouying
Department of TCM Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100102, China.
Open Life Sci. 2020 Jul 3;15(1):449-457. doi: 10.1515/biol-2020-0053. eCollection 2020.
A pharmacokinetic comparison was made to evaluate the influence from other components in the Extract on pharmacokinetic behavior of Puerarin. Samples of blood and brain were collected by microdialysis and determined by high-performance liquid chromatography-mass spectrometry (MS)/MS. Pharmacokinetic parameters were estimated from the concentration versus time data using non-compartmental methods. In addition, a comparative pharmacokinetic study of Puerarin in stroke rats was studied after administration of the Extract via different routes to find an effective way to deliver drug into brain. Obvious pharmacokinetic differences were also observed in comparison between the Puerarin group and the Extract group based on middle cerebral artery occlusion (MCAO) rats. The and area under the curve (AUC) of Puerarin in olfactory bulb of the Extract group significantly reduced when it was intravenously administered. However, the AUCs of Puerarin in plasma are 134.72 and 1707.02 mg/L min, via intranasal and intravenous administration of the Extract, respectively. The AUC of the intranasal group in brain is seven times higher than that of intravenous administration. Other ingredients in the Extract may affect the disposition of Puerarin and its transportation through the blood-brain barrier via intravenous administration. But intranasal administration is an effective route to deliver isoflavone-C-glycoside with poor hydrophilicity into brain.
进行了药代动力学比较,以评估提取物中其他成分对葛根素药代动力学行为的影响。通过微透析收集血液和脑组织样本,并采用高效液相色谱-质谱联用(MS)/MS进行测定。使用非房室模型方法根据浓度-时间数据估算药代动力学参数。此外,研究了通过不同途径给予提取物后,葛根素在中风大鼠中的比较药代动力学,以寻找将药物输送到脑内的有效途径。基于大脑中动脉闭塞(MCAO)大鼠,在葛根素组和提取物组之间的比较中也观察到了明显的药代动力学差异。提取物组静脉注射时,嗅球中葛根素的半衰期(t1/2)和曲线下面积(AUC)显著降低。然而,通过鼻内和静脉注射提取物,血浆中葛根素的AUC分别为134.72和1707.02mg/L·min。鼻内给药组在脑中的AUC比静脉给药组高7倍。提取物中的其他成分可能会影响葛根素的处置及其通过静脉给药穿过血脑屏障的运输。但是鼻内给药是将亲水性差的异黄酮-C-糖苷输送到脑内的有效途径。