Effects Of KDZ On The Pharmacokinetics Of The Drug Xueshuantong Saponins

Xueshuantong and Kudiezi injection play an important role on the treatment of ischemic cerebrovascular disease in clinical. In this paper, pharmacokinetic effect of Kudiezi injection on notoginsenoside R1, ginsenoside Rg1, Re, Rb1and Rd in normal and middle cerebral artery occlusion-reperfusion rats was studied. The main research contents and results are as follows:1. Establishment of a quantification method for five saponins in rat plasma.The quantification of notoginsenoside R1, ginsenoside Rg1, Re, Rb1and Rd in rat plasma was performed by ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-MS/MS). Plasma samples were precipitated with acetonitrile. The separation was performed on a Waters BEH C18column (2.1mm×50mm,1.7μm) with a gradient of water and acetonitrile in5.5min. The analysis method was successully applied in pharmacokinetic study of5saponins.2. Pharmacokinetic effect of Kudiezi injection on five saponins in normal rats.Eighteen rats were randomly divided into three groups:rats in group A and B received an intravenous administration of Kudiezi injection and Xueshuantong with a dose of4.2mL·kg-1and46.6mg·kg-1in a different order, respectively. Rats in group C only received an intravenous administration of Xueshuantong with a dose of46.6mg·kg-1.Ginsenoside Rd and Rb1eliminated slowly, however, notoginsenoside R1, ginsenoside Re and Rg1eliminated quickly. In comparisons with administration of Xueshuantong powder alone, the pharmacokinetic parameters were dramatically different. The AUC0→t of ginsenoside Rd and Rb1markedly decreased, and CL increased. The t1/2of ginsenoside Rb1decreased. The MRT0→t of ginsenoside Re, Rg1, Rd and notoginsenoside R1significantly reduced, the Vd of ginsenoside Rd also significantly decreased. In addition to MRT0→t, other pharmacokinetic parameters of notoginsenoside R1showed no significant difference statistically.3. The effect of compatibility with Kudiezi injection on the pharmacokinetic parameter values of five saponins in middle cerebral artery occlusion-reperfusion rats.The intraluminal thread was inserted into the internal carotid artery in rat to achieve an animal model of reversible middle cerebral artery occlusion. The same operation was done to the model group except insertion of the intraluminal thread. In this part, the effect of compatibility with Kudiezi injection on the pharmacokinetic parameter values of notoginsenoside R1, ginsenoside Rg1, Re, Rb1and Rd in middle cerebral artery occlusion-reperfusion rats. The results showed that with the compatibility of Kudiezi injection, the exposure level of five saponins in Xueshuantong was generally lower in rats.In comparisons with administration of Xueshuantong powder in normal rats, the pharmacokinetic parameters in middle cerebral artery occlusion-reperfusion rats were dramatically different. Cmax of notoginsenoside R1increased, the MRTo0→t of ginsenoside Re decreased, and CL increased. The t1/2and MRT0→t of ginsenoside Rb1decreased. The t1/2, MRTo0→t and Vd of ginsenoside Rd significantly reduced, other pharmacokinetic parameters showed no significant difference statistically.