齐墩果酸与二氢齐墩果酸灌胃及静脉注射给药后在大鼠体内的药动学研究  

Study on the Pharmacokinetics of Oleanolic Acid and Dihydrooleanolic Acid by Intragastric Administration and Intravenous Injection in Rats in vivo

作　　者：陈瑞[1] 李维[1] 李永[1] 刘瑶[1] 黄静[1] 汤磊[1] 

机构地区：[1]贵州医科大学医药卫生管理学院,贵阳550004

出　　处：《中国药房》2017年第13期1777-1780,共4页China Pharmacy

摘　　要：目的:研究齐墩果酸及其衍生物二氢齐墩果酸ig及iv给药在大鼠体内的药动学及绝对生物利用度。方法:12只SD大鼠随机分为齐墩果酸给药组和二氢齐墩果酸给药组,每组6只,两组大鼠均ig给药(50 mg/kg),1周后于尾iv给药(2 mg/kg)。分别于给药前及给药后(ig为0.1、0.25、0.5、0.75、1、1.5、2、3、5、7、9、12 h,iv为0.05、0.15、0.25、0.5、0.75、1、2、3、5、7、9、12 h)尾静脉取血0.3 mL,采用超高效液相色谱(UPLC)-四级杆串联飞行时间质谱法(QTOF)测定血药浓度,DAS 2.0药动学软件计算药动学参数与绝对生物利用度。结果:大鼠ig与iv齐墩果酸后,AUC_(0-∞)分别为(232.10±7.17)、(1 203.99±19.65)ng·h/mL,t1/2分别为(1.75±0.10)、(1.41±0.04)h;ig给药后c_(max)为(121.3±18.92)ng/mL,t_(max)为(0.54±0.10)h,绝对生物利用度为0.77%。大鼠ig与iv二氢齐墩果酸后,AUC_(0-∞)分别为(382.03±23.73)、(386.14±10.65)ng·h/mL,t_(1/2)分别为(2.47±0.45)、(1.44±0.03)h;ig给药后c_(max)为(124.52±12.28)ng/mL,t_(max)为(0.63±0.14)h,绝对生物利用度为3.96%。结论:在大鼠体内,二氢齐墩果酸的绝对生物利用度显著高于齐墩果酸。OBJECTIVE：To study the pharmacokinetics and absolute bioavailability of oleanolic acid and its derivative di-hydrooleanolic acid in rats in vivo. METHODS：12 SD rats were randomly divided into oleanolic acid administration group and di-hydrooleanolic acid administration group,6 in each group. All rats were intragastrically given related medicine（50 mg/kg）,then in-travenously injected related medicine（2 mg/kg）in tail vein after 1 week. Sample blood 0.3 mL was taken from tail vein before ad-ministration and after administration（0.1,0.25,0.5,0.75,1,1.5,2,3,5,7,9,12 h for ig;0.05,0.15,0.25,0.5,0.75,1, 2,3,5,7,9,12 h for iv）. UPLC-QTOF was conducted to determine the plasma concentration,and DAS 2.0 pharmacokinetic software was used to calculate pharmacokinetic parameters and absolute bioavailability. RESULTS：After ig and iv oleanolic acid, the AUC0-∞ were（232.10±7.17）,（1203.99±19.65）ng·h/mL,t1/2 were（1.75±0.10）,（1.41±0.04）h respectively;after ig,cmax was （121.3 ± 18.92） ng/mL,tmax was （0.54 ± 0.10） h,absolute bioavailability was 0.77%. After ig and iv dihydrooleanolic acid, AUC0-∞ were（382.03±23.73）,（386.14±10.65）ng·h/mL,t1/2 were（2.47±0.45）,（1.44±0.03）h;after ig,cmax was（124.52± 12.28）ng/mL,tmax was（0.63±0.14）h,absolute bioavailability was 3.96%. CONCLUSIONS：The absolute bioavailability of di-hydrooleanolic acid is significantly higher than oleanolic acid in rats.

关 键 词：齐墩果酸 二氢齐墩果酸 大鼠 超高效液相色谱-四级杆串联飞行时间质谱法 药动学 生物利用度 

分 类 号：R917[医药卫生—药物分析学]