异甜菊醇在大鼠离体肝灌流中的药代动力学研究  

Isosteviol pharmacokinetics in isolated rat liver perfusion

作　　者：张如洪[1] 邹军[1] 李丹[1] 

机构地区：[1]武汉大学人民医院药学部,湖北武汉430060

出　　处：《中国医药导报》2013年第30期144-147,共4页China Medical Herald

摘　　要：目的研究异甜菊醇在大鼠肝脏内的代谢情况。方法给予SD大鼠离体肝灌流（112）行异甜菊醇的初步药动学研究（体外试验）。分离5只大鼠肝脏然后用含有异甜菊醇的介质进行循环灌流，在时间为0、1、3、5、10、15、20、25、30、40、50、60rain时收集灌流液样品，每间隔10min收集胆汁样品，样品用HPLC—UV分析。尿液（前面实验收集）、灌流液和胆汁样品用β-葡萄糖醛酸酶（1-3U／μL）培养再进行HPLC—UV分析。结果40～50min后的灌流液中，HPLC法检测不到异甜菊醇，而胆汁中完全没有检测到。灌流液和胆汁分别经过β-葡萄糖醛酸酶／硫酸根培养后，色谱方法与灌流液的一样保持不变，胆汁样品中得到了明显的异甜菊醇峰。60min中的药动学参数正T1/2、AUClast、Vz（ods）、CLH、EH（肝脏提取率）和回收率（R0-60代谢率）分别为：（17．82±2．5）min、（258．18±33．2）min·μg／mL、（425．35±32．1）mL、（17．7±2．2）mL／min、（0．59±0．07）和（18．08±2．5）。结论经过40—50min灌流后异甜菊醇主要在肝脏中积累，以葡萄苷酸化形式从胆汁排泄，很可能大部分经过胆汁排泄慢慢的消除到粪便中。Objective To perform research on hepatic handling of isosteviol in isolated rat liver. Methods Preliminary phar- maeokinetie investigation was performed in isolated liver perfusion （ILP） in Sprague-Dawley （SD） rats （in vitro study）. 5 rat livers were isolated and perfused in a recirculating system with medium containing isosteviol. Perfusate samples were collected at t = 0, 1, 3, 5, 10, 15, 20, 25, 30, 40, 50 and 60 min, and bile samples were collected every 10 min. Samples were ana- lyzed by HPLC-UV. The collected urine （from previous study）, perfusate and bile samples were incubated with β-glu- euronidase （1.3 U/μL） and then analyzed by HPLC-UV. Results Isosteviol became undeteetable after 40 to 50 minutes in perfusate by using HPLC method, no isosteviol could be detected in bile. After incubation both perfusate and bile with 15-glu-euronidase/sulphate respectively, chromatographic performance remained the same in perfusate, however obvious peak of isosteviol was obtained in bile. Pharmacokinetie parameters T1/2, AUClast,Vz（obs）, CLH, EH （hepatic extraction ratio） and isosteviol recovery ratio within 60 minutes （R0-60： metabolite ratio） were： （17.82±2.5） rain, （258.18±33.2） min·μg/mL, （425.35±32.1） mL, （17.7±2.2） mL/min, （0.59±0.07） and （18.08±2.5） separately. Conclusion Isosteviol mainly accumulates in the liver after 40-50 min perfusion, it goes into bile as glueuronidate and probably get into faeces via biliary excretion gradually.

关 键 词：异甜菊醇 离体肝灌流 结合物 

分 类 号：R972[医药卫生—药品]