异嗪皮啶在大鼠体内的药物动力学研究及其组织分布  

Studies on Pharmacokinetics and Distribution of Isofraxidin in Rats

作　　者：范婷 李倩[1] 姚欢 Fan Ting;Li Qian;Yao Huan(Department of Pharmacy,Honghui Hospital,Xi’an Jiaotong University,Xi’an 710054,China;Department of Pharmacy,Xianyang Central Hospital)

机构地区：[1]西安交通大学附属红会医院药剂科,西安710054 [2]咸阳市中心医院药学部

出　　处：《中国药师》2020年第12期2371-2377,共7页China Pharmacist

摘　　要：目的:建立HPLC方法对异嗪皮啶在大鼠体内的药物动力学及组织分布进行研究。方法:以4-羟基香豆素为内标,通过HPLC检测血浆样品和各组织样品中的药物的含量:采用Diamonsil C18色谱柱(150×4.6 mm,5μm);流动相为乙腈-0.1%磷酸(20∶80);紫外检测波长为344 nm;柱温设定在30℃;流速为1.0 ml·min-1。并利用药动学软件3p97计算各药物动力学参数。结果:本法灵敏度较高,所制备的样品中杂质干扰较小,而且操作简便。异嗪皮啶主要药动学参数:tmax=(0.27±0.02)h,Cmax=(7.52±0.47)μg·ml-1,t1/2=(4.35±0.73)h,AUC0→12=(13.74±1.01)μg·ml-1·h,CL/f(s)=(1.89±0.07)mg·kg·h-1(μg·ml-1),V/f(c)=(1.37±0.04)(mg·kg-1)/(μg·ml-1)。异嗪皮啶给药30 min后体内分布较广,以脑中浓度最高,约为肺中浓度的3倍;脾中含量次之,心、肝、肺、肾中含量相当;120 min后药物浓度均明显降低。结论:异嗪皮啶C-t曲线为一室模型;异嗪皮啶在大鼠体内分布较广,但浓度普遍较低,给药120 min后药物浓度均明显降低。Objective:To establish an HPLC method for the analysis of pharmacokinetics and distribution of isofraxidin (IF) in rats.Methods:With 4-hydroxycoumarin as the internal standard,the drug contents in plasma samples and tissue samples were determined by HPLC.The analysis was performed on a Diamonsil C18column (4.6 mm×150 mm,5μm).The mobile phase was acetonitrile with 0.1%phosphoric acid aqueous solution (20∶80).The flow rate and detection wavelength was set at 1.0 ml·min-1and 344 nm,respectively,and the column temperature was 30℃.The pharmacokinetic parameters were processed by 3P97 software.Results:This method had higher sensitivity,less interference of impurities in the prepared samples,and was easy to operate.The concentration-time profile of IF fit a one-compartment model.The major pharmacokinetic parameters of IF in rats were as follows:tmaxwas (0.27±0.02) h,Cmaxwas (7.52±0.47)μg·ml-1,t1/2was (4.35±0.73) h,AUC0→12was (13.74±1.01)(μg·ml-1)×h,CL/f(s)was (1.89±0.07)mg·kg-1·h-1(μg·ml-1) and V/f(c)was (1.37±0.04)(mg·kg-1)/(μg·ml-1).Conclusion:C-t Curve of IF is a one-chambe model.IF is midely distribute in rats with lower concentration,and the drug concentrations in all organs is significantly ruduced at 120 min after oral administration.

关 键 词：异嗪皮啶 高效液相色谱 药物动力学 组织分布 

分 类 号：R969.1[医药卫生—药理学]