Pharmacokinetics and brain distribution differences of baicalin in rat underlying the effect of Panax notoginsenosides after intravenous administration  

作　　者：YANG Yan-Fang LI Zhi XIN Wen-Feng WANG Yong-Yan ZHANG Wen-Sheng 

机构地区：[1]State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University [2]School of Pharmaceutical Science, Peking University [3]Engineering Research Center of Natural Medicine,Ministry of Education [4]College of Resources Science & Technology, Beijing Normal University [5]Engineering Research Center of Sanqi Biotechnology and Pharmaceutical

出　　处：《Chinese Journal of Natural Medicines》2014年第8期632-640,共9页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81274118);the Key New Drug Creation and Development Program of China(No.2012 ZX09103-201);the National Key Technology R&D Program(No.2012BAI29B08)

摘　　要：Baicalin(BA) is the most well-known flavonoid present in Radix Scutellariae. The aim of this study was to explore whether the pharmacokinetic behavior of BA in rat brain can be affected by Panax notoginsenosides(PNS), and to assess the possible mechanism for the observed effects. Specific HPLC and HPLC/MS/MS methods were developed and validated for the determination of BA in the rat plasma and brain using carbamazepine as an internal standard. BA was found to enter rat brain quickly after a single intravenous dose. When co-administered with PNS, clearance(CL) of BA from rat plasma decreased by 50.00%, while the area under the curve AUC0-t and AUC0-∞ increased 94.69% and 87.68%, respectively. On the other hand, some pharmacokinetic parameters of BA in rat brain had obvious differences after PNS was administered, such as an increase in Tmax from 5 min to 15 min, an increase in AUC0-t and AUC0-∞ by 42.75% and 29.39%, respectively, as well as a decrease in CL by 27.95%. Together, these results indicate that PNS can decrease the elimination rate of BA from rat plasma, promote the penetration of BA into rat brain, increase the concentration and slow down the elimination of BA from rat brain. The data provide important information that compatibility with PNS can promote the consequent effects of BA for the treatment of encephalopathy.Baicalin（BA） is the most well-known flavonoid present in Radix Scutellariae. The aim of this study was to explore whether the pharmacokinetic behavior of BA in rat brain can be affected by Panax notoginsenosides（PNS）, and to assess the possible mechanism for the observed effects. Specific HPLC and HPLC/MS/MS methods were developed and validated for the determination of BA in the rat plasma and brain using carbamazepine as an internal standard. BA was found to enter rat brain quickly after a single intravenous dose. When co-administered with PNS, clearance（CL） of BA from rat plasma decreased by 50.00%, while the area under the curve AUC0-t and AUC0-∞ increased 94.69% and 87.68%, respectively. On the other hand, some pharmacokinetic parameters of BA in rat brain had obvious differences after PNS was administered, such as an increase in Tmax from 5 min to 15 min, an increase in AUC0-t and AUC0-∞ by 42.75% and 29.39%, respectively, as well as a decrease in CL by 27.95%. Together, these results indicate that PNS can decrease the elimination rate of BA from rat plasma, promote the penetration of BA into rat brain, increase the concentration and slow down the elimination of BA from rat brain. The data provide important information that compatibility with PNS can promote the consequent effects of BA for the treatment of encephalopathy.

关 键 词：BAICALIN Panax notoginsenosides Rat plasma Rat brain PHARMACOKINETICS HPLC/MS/MS 

分 类 号：R969.1[医药卫生—药理学]