三苯双脒在大鼠血浆和胆汁中代谢动力学研究

摘要/Abstract

摘要：

目的研究三苯双脒在大鼠血浆和胆汁中的药物代谢动力学。方法 20只雄性SD大鼠随机分为对照组和给药组（每组10只）。给药组大鼠经口灌胃三苯双脒（200 mg/kg）：其中5只大鼠于给药后0.5、1.0、2.0、3.0、4.0、5.0、6.0、8.0、10.0、24.0和36.0 h取眼眶血;另5只大鼠给药后,收集0.5~1.0、1.0~1.5、1.5~2.0、2.0~2.5、2.5~3.0、3.0~3.5、3.5~4.0、4.0~4.5、4.5~5.0、5.0~5.5、5.5~6.0、6.0~6.5、6.5~7.5、7.5~8.5、8.5~9.5、9.5~10.5 h的胆汁;对照组大鼠不给药,其中5只大鼠与给药组相同时间下同步取眼眶血,另5只大鼠与给药组相同时间下同步收集胆汁。优化高效液相色谱检测条件,测定大鼠血浆和胆汁中对-（1-二甲氨基乙亚氨基）苯胺（简称氨脒）的浓度,绘制血药浓度-时间曲线、胆汁药物浓度-时间曲线以及胆汁排泄速率和积累排泄量曲线。结果氨脒在血浆中的达峰时间（T_max）为（0.9 ± 0.2）h,血药峰浓度（C_max）为（8.1 ± 2.1）mg/L;氨脒在胆汁中的T_max为（1.2 ± 0.4）h,胆汁药物C_max为（11.2 ± 2.1）mg/L。大鼠给药后0.5~3.0 h的胆汁排泄速率最快,11 h内胆汁中氨脒的累积排泄量为（40.1 ± 12.0）μg,氨脒累积排泄率为0.57‰。结论三苯双脒代谢产物氨脒在大鼠胆汁中的平均浓度高于在血浆中的浓度,且滞留时间较长,有利于杀灭寄生于胆道中的华支睾吸虫。

关键词: 三苯双脒, 对-（1-二甲氨基乙亚氨基）苯胺, 代谢动力学, 血浆, 胆汁, 华支睾吸虫

Abstract:

Objective To study the pharmacokinetics of tribendimidine in rat plasma and bile. Methods Twenty male Sprague Dawley rats were randomly assigned into control and tribendimidine groups (n = 10 in each). Rats in the tribendimidine group were further divided into two batches after oral gavage of 200 mg/kg tribendimidine: 5 were used for orbital blood collection at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 24.0 and 36.0 h after administration, while the other 5 were used for bile collection at 0.5-1.0, 1.0-1.5, 1.5-2.0, 2.0-2.5, 2.5-3.0, 3.0-3.5, 3.5-4.0, 4.0-4.5, 4.5-5.0, 5.0-5.5, 5.5-6.0, 6.0-6.5, 6.5-7.5, 7.5-8.5, 8.5-9.5, and 9.5-10.5 h. Rats in the control group received same operations except that no tribendimidine was administered. After optimizing HPLC detection conditions, concentrations of p-（1-dimethylamino ethylimino） aniline （dADT） in rat plasma and bile were measured. The concentrations were plotted against time, and curves for bile excretion rate and cumulative excretion were drawn. Results The time for maximum dADT （T_max） and the maximum concentration of dADT （C_max） in plasma were （0.9 ± 0.2） h and （8.1 ± 2.1） mg/L, respectively, and those in the bile were （1.2 ± 0.4） h and （11.2 ± 2.1） mg/L, respectively. The bile excretion rate was highest during 0.5-3.0 h after administration, and the cumulative excretion quantity of dADT was（40.1 ± 12.0） μg within 11 h, with a cumulative excretion rate of 0.57‰. Conclusion The tribendimidine metabolite dADT shows a higher concentration and a longer stay in the bile than in the plasma, which may be beneficial for the treatment of Clonorchis sinensis that parasitizes in the biliary tract.

Key words: Tribendimidine, P-（1-dimethylamino ethylimino）aniline, Pharmacokinetics, Plasma, Bile, Clonorchis sinensis

中图分类号:

R383.22

姜斌, 陶奕, 徐莉莉, 霍乐乐, 魏玉芬, 刘妮, 殷梦, 张皓冰. 三苯双脒在大鼠血浆和胆汁中代谢动力学研究[J]. 中国寄生虫学与寄生虫病杂志, 2018, 36(5): 449-454.

Bin JIANG, Yi TAO, Li-li XU, Le-le HUO, Yu-fen WEI, Ni LIU, Meng YIN, Hao-bing ZHANG. Pharmacokinetics of tribendimidine in rat plasma and bile[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2018, 36(5): 449-454.

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