白藜芦醇苷及其代谢物在Beagle犬体内的排泄动力学研究

摘要

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.%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.