没食子酸在大鼠体内的药物动力学特征及生物利用度研究  

Study on pharmacokinetics and bioavailability of gallic acid in rats

作　　者：朱钰璞 张维敏 武坤 王四旺 余喆 李骅 ZHU Yupu;ZHANG Weimin;WU Kun;WANG Siwang;YU Zhe;LI Hua(Cadet Corps of School of Basic Medicine,Air Force Medical University,Xi′an 710032,China;Department of Pharmacy,the 518 th Hospital of PLA,Xi′an 710043,China;Department of Chinese Materia Medica and Natural Medicines,School of Pharmacy,Air Force Medical University,Xi′an 710032,China;Department of Pharmaceutical Analysis,School of Pharmacy,Air Force Medical University,Xi′an 710032,China)

机构地区：[1]空军军医大学基础医学院学员大队,西安710032 [2]解放军第518医院药剂科,西安710043 [3]空军军医大学药学系中药与天然药物学教研室,西安710032 [4]空军军医大学药学系药物化学与药物分析学教研室,西安710032

出　　处：《西北药学杂志》2021年第3期430-434,共5页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:81703737);陕西省重点研发计划项目(编号:2020SF-209);陕西省自然科学基金项目(编号:2016JQ8035)。

摘　　要：目的建立大鼠血浆中没食子酸的含量测定方法,考察单次不同剂量给药后没食子酸在大鼠体内的药物动力学特征及生物利用度。方法大鼠分别经单次灌胃(50、100、200 mg·kg^(-1))和静脉注射(10 mg·kg^(-1))给予没食子酸,采用高效液相色谱(HPLC)法测定不同时间点的血浆药物质量浓度,用DAS2.1软件拟合分析血浆药物质量浓度-时间数据并计算生物利用度。结果血浆中没食子酸质量浓度在0.025~10.000μg·mL^(-1)范围内具有良好的线性关系(r=0.9999);大鼠分别灌胃给予50、100、200 mg·kg^(-1)没食子酸后,主要药物动力学参数达峰质量浓度(Cmax)分别为(0.83±0.15)、(1.71±0.29)、(3.13±0.56)μg·mL^(-1),达峰时间(tmax)分别为(90.00±21.21)、(85.00±12.25)、(93.75±9.92)min,半衰期(t1/2)分别为(153.65±19.45)、(186.67±23.97)、(150.96±12.70)min,血药质量浓度-时间曲线下面积(AUC0~t)分别为(137.07±24.75)、(262.55±22.05)、(501.64±31.64)mg·min·L^(-1);大鼠静脉注射给予10 mg·kg^(-1)没食子酸后,主要药物动力学参数Cmax为(7.87±0.96)μg·mL^(-1),tmax为(2.00±0.00)min,t1/2为(68.31±7.58)min,AUC0~t为(178.40±44.89)mg·min·L^(-1);没食子酸在大鼠体内的口服绝对生物利用度为14.71%。结论建立的HPLC法用于没食子酸的药物动力学和生物利用度研究简便可靠。单次给药后没食子酸在大鼠体内的药物动力学过程符合一级动力学模型,口服绝对生物利用度较低。Objective To establish a method for the determination of gallic acid(GA)in rat plasma,and to investigate the pharmacokinetics and bioavailability of GA in rats after single administration of different doses.Methods Rats were treated by oral administration of GA at doses of 50,100 and 200 mg·kg^(-1) or by injected at a dose of 10 mg·kg^(-1),respectively.Quantification of GA in rat plasma was achieved by using a simple and rapid HPLC method according to the different time points.The pharmacokinetic parameters of GA were analyzed through plasma concentration-time profiles by using Drug and Statistics version 2.1.Results The linear relationship was good for GA within the range of 0.025-10.000μg·mL^(-1)(r=0.9999).The main pharmacokinetic parameters of GA after oral dosing 50,100 and 200 mg·kg^(-1) were Cmax(0.83±0.15),(1.71±0.29)and(3.13±0.56)μg·mL^(-1),tmax(90.00±21.21),(85.00±12.25)and(93.75±9.92)minutes,t1/2(153.65±19.45),(186.67±23.97)and(150.96±12.70)minutes and AUC0-t(137.07±24.75),(262.55±22.05)and(501.64±31.64)mg·min·L^(-1),respectively.The main pharmacokinetic parameters of GA after intravenous dosing 10 mg·kg^(-1)were Cmax(7.87±0.96)μg·mL^(-1),tmax(2.00±0.00)min,t1/2(68.31±7.58)minutes and AUC0-t(178.40±44.89)mg·min·L^(-1).The oral absolute bioavailability of GA was 14.71%in average.Conclusion The established HPLC method is simple and reliable for the pharmacokinetics and absolute bioavailability study of GA.The pharmacokinetics of GA in rats after single dosing conforms to the first-order kinetic model and lower absolute bioavailability was found after oral dosing.

关 键 词：没食子酸 药物动力学 生物利用度 高效液相色谱法(HPLC) 

分 类 号：R945[医药卫生—微生物与生化药学]