去甲斑蝥素理化性质测定及大鼠在体肠吸收动力学研究

Study on the Physicochemical Properties and the Intestinal Absorption Kinetics of Norcantharidin in Rats

目的测定去甲斑蝥素理化性质及在体肠吸收动力学,为设计缓释制剂提供参考依据。方法测定去甲斑蝥素溶解度、油水分配系数。采用大鼠在体回流方法,利用紫外分光光度法和HPLC分别测定酚红和去甲斑蝥素的含量,研究去甲斑蝥素在不同浓度和不同小肠区段下的吸收。结果去甲斑蝥素在十二指肠、空肠、回肠、结肠的吸收速率常数分别为:0.1623,0.1260,0.0084,0.0035h-1;在小肠的吸收速率常数不同药物浓度70、80、90μg.mL-1时分别为:0.0112,0.0056,0.0071h-1。结论不同的药物浓度对去甲斑蝥素在大鼠全肠道的吸收无显著影响,药物的吸收呈一级动力学过程,吸收机制为被动扩散,提示适于制备日服一次的缓释给药系统。

Objective To investigate physicochemical properties and the absorption kinetics of norcantharidin（NCTD） at different intestine segments in rats. Methods The dissolubility and n-octyl alcohol/water partition coefficient were determined. The intestine in rats was cannudated for in situ recirculation, UV and HPLC were respectively used to determine the concentrations of UV spectrums of phenol red and NCTD. The absorption of NCTD was studied at different intestine segments, and with different concentration of NCTD. Results The absorption rate constants（Ka） at duodenum, jejunum, ileum, and colon were 0.1623, 0.1260, 0.0084, 0.0035h-1 respectively. Ka from intestine at NCTD concentration of70, 80, 90μg·mL-1 were 0.0112, 0.0056, 0.0071h-1 respectively. Conclusion The concentration of NCTD had no distinctive effect on the absorption kinetics. The absorption of NCTD was a first-order process with passive diffusion mechanism, which indicated that NCTD could be prepared as sustained-release dosage form for administration once a day.