1,3-二苯-1,3-丙二酮在小鼠体内的组织分布  

Tissue distribution of 1,3-diphenyl-1,3-propanedione in mice

作　　者：田寒梅 崔蓉[2] 何月莹[3] 吕艳[3] 张宝旭[3] 

机构地区：[1]北京市预防医学研究中心,北京100013 [2]北京大学公共卫生学院劳动卫生与环境卫生学系,北京100191 [3]北京大学公共卫生学院毒理学系,北京100191

出　　处：《北京大学学报（医学版）》2012年第3期437-443,共7页Journal of Peking University:Health Sciences

基　　金："重大新药创制"科技重大专项(2009ZX09103-007)资助~~

摘　　要：目的:研究1,3-二苯-1,3-丙二酮(1,3-diphenyl-1,3-propanedione,DPPD)在小鼠体内各组织中的分布特征。方法:雄性ICR小鼠灌胃给予DPPD后,于不同时间点采集小鼠肝、心、脾、肺、肾及肌组织,以高效液相色谱法(high performance liquid chromatography,HPLC)测定各组织中DPPD的浓度。Thermo Kinetica 4.4.1软件计算药物代谢动力学参数。结果:灌胃给予小鼠DPPD后,DPPD浓度在肝、肾组织中较高(肝AUCtot=41.92μg.h/g,肾AUCtot=40.40μg.h/g),给药后肝、肺组织内的药物浓度迅速达到最大值,Tmax分别为0.32 h和0.33 h,而肌组织的药物浓度则在3.85 h时才达到最大值。DPPD在肝内浓度的最大值Cmax=31.20μg/mL,该浓度值亦为所有受检组织中的最高浓度。给药后24 h仍能在各组织中检测到较低浓度的DPPD。结论:DPPD在各组织中分布不均,肝、肾和肌组织中药物分布量较大,而肺、脾组织中分布较少,且各组织中药物浓度的动态变化规律也各不相同。Objective：To investigate tissue distribution characteristics of 1,3-diphenyl-1,3-propanedione （DPPD） in mice. Methods： Male ICR mice were dosed with DPPD 500 mg/kg via oral gavage, and the tissue samples of the heart, liver, spleen, lungs, kidneys and muscle of each mouse were collected as scheduled. At each time point, the concentrations of DPPD in the mouse tissues were measured by high performance liquid chromatography （HPLC） method. The main pharmaeokinetie parameters were calcu- lated by Thermo Kinetica 4.4.1 software. Results ： DPPD was absorbed rapidly after oral administration. The concentrations of DPPD in the liver and in the kidney were higher, respectively （liver： AUCtot = 41.92μg · h/g, kidney： AUCtot = 40.40 μg · h/g）. The drug concentrations showed a rapid distribution in the liver and lungs （Tmax =0.32 h and 0.33 h respectively） after oral administration, but in the muscle the maximum was 3.85 h. The maximum concentration of DPPD was in the liver （ Cmax = 31.20 μg / g）, which was also the highest tissue concentration of all the subjects. DPPD could be detected at the low concentration within 24 h in all the tissues involved. Conclusion： DPPD distributed unevenly in various tissues. In the liver, kidney and muscle, the amount of the drug concentration was larger, and was lower in the lungs and spleen.

关 键 词：1 3-二苯-1 3-丙二酮 组织分布 药代动力学 小鼠 

分 类 号：R969.1[医药卫生—药理学]