R—hap在大鼠体内的组织分布，排泄及药动学研究

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^125I-R-hap的组织分布，尿、粪及胆汁的排泄情况。^125I-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。

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

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.