盐酸氯米帕明大鼠在体肠吸收动力学研究

Study on in situ intestinal absorption of clomipramine hydrochloride in rats

目的研究盐酸氯米帕明在大鼠肠道的吸收特性。方法采用大鼠在体肠灌流实验方法,利用高效液相色谱法同时测定肠回流液中药物及酚红的浓度,通过酚红的浓度校正相应时刻供试液的体积。结果盐酸氯米帕明浓度为5、10、25μg/ml时小肠的吸收速率常数(ka)为(0.74±0.04)、(0.78±0.03)、(0.77±0.05)h-1;在十二指肠、空肠、回肠和结肠的ka分别为(0.590±0.026)、(0.670±0.032)、(0.680±0.030)和(0.560±0.031)h-1。结论盐酸氯米帕明在大鼠肠道均有良好的吸收。盐酸氯米帕明在小肠的吸收呈表观一级动力学过程,吸收机制为被动扩散。

Objective To investigate the intestinal absorption characteristics oi clomlpramme hydrochlonde in different intestine segments of rats. Methods The in situ intestinal absorption of clomipramine hydrochloride was studied by in situ recirculation perfusion technique. The concentrations of clomipramine hydrochloride and phenol red in the perfusate were determined simultaneously by reversed-phase HPLC. Phenol red was used to calibrate the volume of the perfusate. Results The absorption rate constant of clomipramine hydrochloride at concentrations of 5, 10, 25 μg/ml were （0.74±0.04）,（0.78±0.03）,（0.77±0.05） h^-1 respectively. At duodenum, jejunum, ileum and colon, the permeability coefficient of clomipramine hydrochloride were （0.590±0.026）, （0.670±0.032）, （0.680±0.030）, （0.560±0.031） h^-1 respectively. Conclusion Clomipramine hydrochloride can be absorbed by the whole intestine segments. The absortion of clomipramine hydrochloride is apparent first-order process with passive diffusion mechanism.