Investigation Of Pharmacokinetics On Silybin Meglumine Salt Injection In Rats

Objective: To establish a HPLC method of silybin meglumine salt in plasma, and observe the distribution of high dose of silybin meglumine salt in rats. Preliminarily studied the pharmacokinetics of silybin meglumine salt in rats to provide reference for the prior period research on the injection.Methods: Plasma sample was collected after intravenous injection at high, medium and low-dose (25,12.5,12.5 mg·kg-1) of Silybin Meglumine salt in rats,then,the Concentracation of Silybin Meglumine salt in plasma sample were determined by HPLC methods.3P97 was used to data processing to calculate pharmacokinetics parameters.The concentration in the plasma of the rats heart ,liver,spleen,lungs and kidney were tested at given time pointafter intravenous injection at high–dose, The plasma protein binding rate of the high, medium ,and low-dose Silybin Meglumine salt of the rat was tested by ultrafiltration.Results: After the screening of the sample disposing methods and detecting condition, A method of determing a micro-dose silybin in plasma and tissue by HPLC was established.The method shows a high sensitivity ,selectivity, accuracy, recovery rate and stability which was all fit for the requirements of this study. As follows are the pharmacokinetics parameters.High-dose: t1/2=38.06min,AUC=1868.367min·μg·mL-1,CL(s)=0.026mL·min-1, K10=0.018; medium-dose: t1/2=24.148min,AUC=1427.284min·μg·mL-1,CL(s)=0.041mL·min-1, K10=0.028; low-dose: t1/2=20.640min, AUC=452.248min·μg·mL-1, CL(s) =0.037mL·min-1, K10=0.033;Plasma protein binding:73.434%(high-dose),72.022%(medium-dose),70.963%(low-dose).Through the comparison among the highest medicine points of the high-dose Silybin Meglumine salt distributing in different tissues,the conclusion is:lungs>liver>kidney>heart>spleen.Conclusion: The results showed an elimination process of nonlinear dynamics character and two-compartment model diatrabution character after High-dose, medium-dose, low-dose injection.The plasma protein binding rates different doses injection were on 70%. After high-dose injection Silybin Meglumine salt can be found in heart,liver spleen,lungs and kidney;and a more distribution was found in liver.