羟基喜树碱的油/水分配系数与大鼠小肠吸收的相关性研究

Study on the relativity of oil/water partition coefficient of hydroxycamptothecin and its absorption coefficiency in small intestines of rats

目的:探讨在不同pH值条件下羟基喜树碱的油/水分配系数与大鼠小肠吸收之间的相关性。方法:缓冲溶液水相pH值依次为2.2、4.0、6.0、7.4、9.16及11,正辛醇为油相,采取"摇瓶法"使药物在油相/水相中达到平衡后,用高效液相测定油/水相中药物的浓度,计算药物的油/水分配系数。以酚红为体积校正剂,测定不同pH值条件下,大鼠小肠吸收系数。将药物油/水分配系数与大鼠小肠吸收系数进行线性回归。结果:药物的油/水分配系数与大鼠小肠吸收系数随分散介质的pH值不同而改变,两者之间的线性关系为:y=0.001 3x+0.009 1,相关系数R2为0.959 7。结论:羟基喜树碱的油/水分配系数与小肠吸收之间存在良好的线性关系,可以油/水分配系数预测大鼠小肠吸收。

AIM： To explore the correlativity of the oil/water partition of hydroxycamptothecin and its absorp-tion coefficiency in small intestine in rats.METHODS： pH value of water phase in buffer solution in turn took 2.2,4.6,7.4,9.6 and 11,while octanol was adopted as oil phase.After phase equilibrium,HPLC was used to determine the concentration of hydro-xycamptothecin,and oil/water partition coefficient was calculated with the phenol red as volume calibration agent,small intestinal absorption coefficients of rats in different pH were plotted against its oil/water partition coefficients.RESULTS： Oil/water partition coefficient（x） of hydroxycamptothecin and small intestinal absorption（y） altered with the change of pH value of the dispension medium.The linear re-gress equation was constructed as y = 0.001 3x ＋ 0.009 1 with its correlation coefficient R2 being 0.959 7.CONCLUSION： There exists a good linear dependence between oil/water partition coefficient of hydroxycamptoth-ecin and its absorption coefficient in small intestines of rats.Oil/water partition coefficient can be used to design the new oral preparations.