Study On Intestinal Absorption Kinetics And Pharmacokinetics Of Baicalin Magnesium Salt And The Influence Of Glucose On Its Absorption

Experiments were performed and proved that baicalin contained in Scutellaria baicalensis Georgi was pre-existed on the form of baicalin magnesium salt.Its water solubility,stability in water and phosphate buffer solution and its anti-inflammatory and antibacterial effects had been studied,but its intestinal absorption kinetics and pharmacokinetics.Therefore,HPLC method was used to determine the content of baicalin magnesium salt in rats plasma and intestinal solution for its intestinal absorption kinetics and pharmacokinetics study,as well as the similarities and differences of absorption between baicalin magnesium salt and baicalin in rats intestine and plasma.At the same time,some reports pointed out that glucose could promote the absorption of MgSO₄ in rat's intestine.Therefore,the effect of glucose on the intestinal absorption of baicalin magnesium salt was investigated,as well as the pharmacokinetics characteristics influenced by glucose.Objective:1.To establish a HPLC method for assay the content of baicalin magnesium salt in rats intestinal solution and plasma,and study the intestinal absorption kinetics and pharmacokinetics characteristics,comparing with that of baicalin.2.To discuss the influence of glucose on absorption of baicalin magnesium salt by intestinal absorption kinetics and pharmacokinetics experiments,and investigated the absorption mechanism of baicalin magnesium salt.Methods:1.Experiments were performed using an Agilent 1260 HPLC to establish methods for the determination of baicalin magnesium salt,and calculated its main parameters of the intestinal absorption kinetics and pharmacokinetics.2.SPIP was conducted to study similarities and differences of baicalin magnesium salt and baicalin on intestinal absorption kinetics.At the same time,the rats were orally administration with BMG and BG to compare the pharmacokinetic characteristics of baicalin magnesium salt and baicalin.3.SPIP was performed to investigate the effect of glucose on the absorption of baicalin magnesium salt.And the absorption mechanism of baicalin magnesium salt was clarified.Simultaneously,BMSM and BMSG were prepared to compare the pharmacokinetic differences of baicalin magnesium salt influenced by glucose.Results:1.A HPLC method was successfully established to assay contents of baicalin magnesium salt,with the mobile phase consisted of acetonitrile-2%formic acid aqueous?77:23,v:v?was used and an Discovery C₁₈ column?250mm×4.6 mm,5?m?.Samples ran at a flow rate of 0.8 mL/min under the detection wavelength of 278 nm.The final injection volume was 10?L and the temperature of column oven was maintained at 37°C.2.In the SPIP experiment,the Abs of baicalin magnesium salt was 2.42times than that of baicalin,but their pharmacokinetic parameters,such as AUC_0-t,C_max,T_max,CL_z and t_1/2,showed no difference?P>0.1?.3.The results of SPIP showed that the higher the baicalin magnesium salt concentrations,the more the intestinal absorption.And there were no significant differences of the Ka and P_app between the high,medium and low concentration groups of baicalin magnesium salt.After the glucose was doubled into the K-R solution,the average Abs of the baicalin magnesium salt at the high,middle and low concentration groups increased by 2.08,1.79and 2.18 times,respectively.At the same time,the pharmacokinetics results showed that the AUC_0-t and the AUC_0-?of baicalin magnesium salt in the BMSG group were 1.32 and 2.67 times than that of baicalin magnesium salt in the BMSM group,which showed significant differences?P<0.05?.Conclusion:1.HPLC method was established successfully to detect the contents of baicalin magnesium salt in rats plasma and intestinal solution.2.The intestinal absorption of baicalin magnesium salt was significantly better than that of baicalin.But the pharmacokinetics of baicalin magnesium salt and baicalin did not show significant differences,that needed further study.3.Glucose can promote the absorption of baicalin magnesium salt,of which mechanism has not been cleared yet and it is worth to be further studied.Meanwhile,the absorption mechanism of baicalin magnesium salt is passive diffusion,and it participates in enterohepatic circulation,and there exist the effect of excretion secretion.