Studies On The Methods For Evaluating Pharmacokinetics And Pharmacodynamics Of Panax Notoginseng Saponins

Pharmacokinetic study of traditional Chinese medicine has important scientific significance. It's a challenging frontier. The main method is to blood collection method, but hypovolaemia will be induced because of excessive loss of blood, so the frequency and volume of blood must be limited. Microdialysis can provide tissue-specific and real-time information of drugs. The dialysate can be analysed directly. Without wasting of biofluids, it can offer continuous sampling. It can be applied to evaluate the drug absorption,, metabolism, distribution and elimination.For the innovation and development of traditional Chinese medicines evaluation methods of pharmacodynamic action, a kind of technology which reflects the global efficacy and its own characteristics of traditional Chinese medicine is needed to be established. Metabonomics, defined as quantitative measurement of dynamic metabolic response to pathophysiological stimuli or genetic modification, has been applied in aspects of pharmacodynamics of traditional Chinese medicine and toxicology.In this thesis, home-made microdialysis probes were applied for the pharmacokinetic analysis of panax notoginseng saponins, its application of pharmacokinetics of traditional Chinese medicine was explored; On the other hand, panax notoginseng saponins was set as an example to evaluate the pharmacodynamics of traditional Chinese medicine, which based on metabonomics. The main contents of this study are listed as follows:(1) In vitro microdialysis experiments were carried out to evaluate the influence of perfusate flow rate, concentration of ginsenoside Rg₁, methods used for determination of relative recovery and stability of membrane on the extraction efficiency of home-made probes. The results revealed that relative recovery declined with the increase in perfusion flow rate. Statistically significant differences about relative recovery were found between forward direction dialysis and retrodialysis. After the home-made probe was implanted and applied to continuously sampling in vivo for 12 h, the permeability of the membrane didn't vary significantly.(2) With home-made probes, tissue-specific and real-time method was established to determine the concentration of freely states of drugs. Liquid chromatography-mass spectrometry was adopted later. After a single dosage of 10 mg/kg (i.v.), the concentrations of ginsenoside Rg₁, Re and notoginsenoside R₁ in dialysate from rat blood were determined, three kinds of saponins eliminated rapidly.(3) A model of acute myocardial ischemia caused by coronary artery ligated and GC-MS method was adopted to analyze the changes of endogenous metabolites, such as amino acids, fatty acids and saccharides from rat serum, before and after modeling. Significant deviation was found between model and normal groups. T-test and variable importance in the projection were adopted to fix 10 biomarkers, an effective reference was provided for the pharmacodynamics of panax notoginseng saponins. These 10 biomarkers from rats' serum of treatment group convergenced to normal group after deep research.