哈巴俄苷及其代谢产物在大鼠体内的药代动力学

Pharmacokinetics of hapagoside and its metabolite in rats

采用LC-MS技术对哈巴俄苷单体给药后在大鼠体内的药动学进行了研究,发现并鉴定其主要代谢产物可能为肉桂酸,在此基础上应用HPLC法测定了哈巴俄苷经口给药或静脉给药后的药代动力学特征。色谱分离采用C18色谱柱(250 mm×4.6 mm,5μm);流动相为甲醇-水-醋酸溶液(60∶40∶0.1),检测波长为279 nm。结果表明,哈巴俄苷经口给药后吸收迅速,达峰后迅速消除,tm ax和t1/2分别为(0.47±0.21)h和(4.96±0.98)h,4 h后血药浓度降至约0.1μg/mL。其代谢产物肉桂酸在给药后迅速出现并缓慢消除,tm ax和t1/2分别为(4.17±1.39)h和(5.78±2.67)h。哈巴俄苷静脉给药后消除迅速,t1/2为(1.89±0.32)h,而肉桂酸的消除速度仍与口服相近,t1/2为(5.16±2.27)h。实验结果显示哈巴俄苷口服吸收迅速,生物利用度低,在大鼠体内可能主要代谢为肉桂酸,后者在给药后迅速出现并缓慢消除。

Cinnamic acid was found and identified as the main metabolite in rat plasma after oral administration of hapagoside.HPLC was used for the evaluation of pharmacokinetics of hapagoside and its main metabolite in rats;and the analytes were chromatographically separated with a C18 column（250 mm×4.6 mm,5 μm）.The mobile phase was composed of methanol-H2O-acetic acid（60 ∶40 ∶0.1） and UV detector was set at 279 nm.After ig administration,the tmax and t1/2 of hapagoside were 0.47 ± 0.21 h and 4.96 ± 0.98 h（at the dose of 50 mg/kg）,respectively.While the tmax and t1/2 of cinnamic acid were 4.17 ± 1.39 h and 5.78 ± 2.67 h.After iv administration,hapagoside was eliminated rapidly（t1/2=1.89 ± 0.32 h）,while the elimination of cinnamic acid was similar to that via ig administration（t1/2=5.16 ± 2.27 h）.This results indicated that hapagoside was rapidly absorbed after ig administration,although its bioavailability was less than 5%.As the main metabolite of hapogoside in rat plasma,cinnamic acid appeared rapidly and eliminated slowly.