Effects Of Danshen Injection On Pharmacokinetic Parameters Of Gliquidone In Diabetic Rats

Objective:Gliquedone,the second generation of sulfonylurea hypoglycemic agents,is widely used in patients with renal dysfunction due to its rapid absorption by the gastrointestinal and without kidney excretion.Salvia has the effect of making blood circulation acceleration,reducing blood glucose and blood lipid.In addition,it also has a protective effect on diabetic nephropathy.These two drugs have common indications and usage result in increased possibility of co-administration.Therefore,the purpose of this paper is to investigate the effect of danshen injection on pharmacokinetics of gliquidone in diabetic rats.Methods:A simple and rapid HPLC method was established to measure the concentration of gliquidone in blood and used for pharmacokinetic of gliquidone in diabetic rats co-administration with Danshen injection.The method of dialysis were used to investigate the influence of Danshen injection on plasma protein binding rate of gliquidone.Then,the effect of Danshen injection on bile excretion of gliquidone were determined by high performance liquid chromatography-mass spectrometry?LC-MS?.In the end,the effect of Danshen injection on the intestinal absorption by setting up a situ intestinal perfusion model in diabetic rats and normal rats.Results:The results of pharmacokinetic parameters of diabetic rats indicated that the combination administration of the Danshen injection and gliquidone could significantly shorten the peak time,increase the maximum drug concentration and the area under the curve,and could significantly reduce the clearance rate.The results of plasma protein binding rate indicated that the plasma protein binding rate of different concentrations of glibenclamide was almost same.Danshen injection in normal concentration did not affect the plasma protein binding rate of gliquidone.When the concentration of Danshen injection reached 750 mg crude drug/mL,the plasma protein binding rate of gliquidone was significantly reduced.The results of bile excretion showed that Danshen injection had no effect on the bile excretion of gliquidone in diabetic rats.The results of intestinal absorption studies in diabetic rats implied that Danshen injection significantly increased the apparent rate K_a and P_apppp in the normal and diabetic rats.Conclusion:Co-administration of Danshen injection and gliquidone could significantly increase the plasma concentration and bioavailability of gliquidone.These may be related with Danshen injection promoting the intestinal absorption of gliquidone.