炎琥宁肠溶微丸在大鼠体内肠吸收及药物动力学实验研究

Intestinal Absorption of Enteric Coating Potassium Sodium Dehydroandroan drographolide Succinate Pellets in Rat and in vivo Pharmacokinetics Study

目的:建立大鼠血浆和肠内容物中炎琥宁含量测定方法,研究炎琥宁肠溶微丸在大鼠体内肠吸收和药物动力学,为炎琥宁口服制剂的研究提供依据。方法:以大鼠为研究对象,灌胃给予炎琥宁肠溶微丸,采用高效液相色谱法测定大鼠灌胃给药后血浆和各肠段内容物中炎琥宁的药物浓度,评价其在大鼠体内的吸收和药动学特性。结果:给药后2 h小肠和大肠中未发现小丸存在,4 h小肠中小丸的数量最多,肠道内容物中炎琥宁含量最高(3593.13μg),血药浓度-时间曲线符合单室模型特征,求得主要药物动力学参数t1/2为2.69 h,Tmax为5 h,Cmax为3.02μg/mL,血药浓度时间曲线下面积为6.42μg.h/mL。结论:炎琥宁在大鼠小肠有较好吸收,制备炎琥宁肠溶微丸口服给药可行。

Objective：To develop a method for determination the content of Potassium Sodium Dehydroandroan drographolide Succinate（PSDS） in rat intestinal contents and plasma and investigate the intestinal absorption of PSDS pellets in rat and in vivo pharmacokinetics of PSDS pellets.Methods：The content of PSDS in rat intestinal contents and plasma was determined by HPLC.In vivo pharmacokinetic properties and intestinal absorption of PSDS pellets in rat were investigated.Results：Two hours after administration,pellets were not found in the small intestine and large intestine,four hours after administration,the largest number of pellets were found in the small intestine and the concentration of PSDS was the highest in the intestinal contents（3593.13 μg）.The characteristics of plasma concentration-time curve was consistent with a single compartment model.The main drug pharmacokinetic parameters were calculated.t1/2,Tmax,Cmax and AUC were 2.69 h,5 h,3.02 μg/mL and 6.42 μg·h/mL,respectively.Conclusion：PSDS has a good absorption in the rat small intestine and it is feasible to prepare PSDS enteric-coated pellets for oral administration.