白藜芦醇苷及其代谢物在Beagle犬体内的排泄动力学研究

Study on the Excretion Pharmacokinetics of Polydatin and Its Metabolite in Beagle Dogs

目的:研究白藜芦醇苷(TRG)及其代谢物在Beagle犬粪样中的代谢与排泄情况,为TRG的新药开发提供实验依据。方法:4只Beagle犬ig TRG 20%聚乙二醇400溶液50 mg/kg,采用液相色谱-质谱联用法鉴定TRG给药后12~24 h粪样中的代谢物,采用高效液相色谱法测定给药后0~12、12~24、24~36、36~48、48~72、72~96 h TRG在粪样中主要代谢物[其苷元白藜芦醇(TR)]以及TR累积排泄率及排泄速率。结果:在犬粪中可测到TR及TR的2个硫酸结合物,其中TR为主要代谢物,未测到TRG。TR在犬粪中排泄速率于给药后12~24 h时最大,达到9.65 mg/h;其累积排泄率为39.3%,相当于TRG给药剂量的67.2%。结论:犬ig TRG后,TRG主要以TR形式从粪中排出体外。

OBJECTIVE： To study the metabolite and excretion of polydatin （Trans-resveratrol-3-O-glucoside, TRG） and its metabolites in Beagle dog feces, and provide experimental basis for the new drug development of TRG. METHODS： 4 Beagle dogs were intragastrically administrated TRG 20% polyethylene glycol 400 solution 50 mg/kg. LC/MS was used to identify the me- tabolites of TRG in dog feces after 12-24 h of administration, and HPLC was adopted to determine the cumulative excretion rate and excretion speed rate of the major metabolite resveratrol （TR） in feces samples after 0-12, 12-24, 24-36, 36-48, 48-72, 72-96 h of administration. RESULTS： TR and two sulfate conjugates of TR were found in dog feces, and TR was a major metabolite, while TRG was undetermined. The excretion speed rate of TR in dog feces was the rapidest after 12-24 h of administration, reach- ing 9.65 mg/h. Its cumulative excretion rate was 39.3%, equivalent to 67.2% of TRG. CONCLUSIONS： After TRG is intragastri- cally administrated to dogs, TRG was mainly excreted in the form of TR via dog feces.