Tissue distribution,excretion and pharmacokinetics of R-hap in rats  

R-hap在大鼠体内的组织分布，排泄及药动学研究(英文)

作　　者：周佳雨[1] 孟志云 窦桂芳 付守廷 华子春[3] 杨翔[3] 刘军 韦利军 张笋华 

机构地区：[1]沈阳药科大学,辽宁沈阳110016 [2]北京输血研究所药物代谢与药代动力学实验室,北京100850 [3]南京大学医药生物技术国家重点实验室,江苏南京210093 [4]常州千红生化制药有限公司,江苏常州213032

出　　处：《Journal of Chinese Pharmaceutical Sciences》2008年第2期106-112,共7页中国药学（英文版）

基　　金：National Natural Sciences Foundation of China(Grant No.30371669);National High Technology Research and Development Program of China(863 Program,Grant No.2003AA2Z347B).

摘　　要：The purpose of this study is to characterize the tissue distribution, excretion and pharmacokinetics profiles of R-hap in healthy Wistar rats. R-hap was radiolabeled by the IODO-GEN method. Tissue distribution and urinary, fecal and biliary excretion patterns of ^125I-R-hap were investigated following a single i.v. bolus injection. Pharmacokinetics properties of ^125I-R-hap were also examined after a single i.v. bolus injection. The trichloroacetic acid （TCA） precipitated radioactivity was widely distributed and rapiclly diminished in most tissues. Kidney contained the highest radioactivity among all organs and the distribution of ^125I-R-hap to fat was minimal. The cumulative excretion of ^125I-R-hap reached 71.81% ± 2.15% of the administered radioactivity at 48 h and 94.71% ± 1.50% at 120 h. Urinary excretion was the dominant route of elimination following i.v. administration, as 80.64% ± 1.47% and 14.07% ± 0.95% of administered radioactivity were recovered in urine and feces, respectively, in intact rats over 120 h. The mean areas under the plasma concentration-time curve was （8818.4 ± 576.1） Bq/h/mL. The results of tissue distribution, excretion and pharmacokinetics of R-hap in rats provided biopharmaceutical basis for the design of future clinical trials.测定R-hap在健康Wistar大鼠体内的组织分布,排泄及药动学参数。R-hap采用IODO-GEN标记,测定单次推注给药后^(125)I-R-hap的组织分布,尿、粪及胆汁的排泄情况。^(125)I-R-hap药动学参数也是在单次推注给药后测定。R-hap在体内广泛分布,在大部分器官中快速消除。其中肾的含量最高,脂肪的含量最低。累计排泄率为71.81%±2.15%(48小时)及94.71%±1.50%(120小时)。经尿排泄为主要的排泄途径,给药后120小时,尿及粪的累计排泄率分别为80.64%±1.47%,14.07%±0.95%。平均给药时曲线下面积为(8818.4±576.1)Bq/h/mL。R-hap的组织分布,排泄及药动学参数的结果为未来的临床试验设计提供了参考依据。

关 键 词：R-hap Tissue distribution EXCRETION PHARMACOKINETICS 

分 类 号：R96[医药卫生—药理学]