20(S)-原人参二醇油水分配系数测定和大鼠在体肠吸收的研究

Apparent Oil/water Partition Coefficient of 20(S)-PPD and Its Intestinal Absorption in Rats

目的测定20(S)-原人参二醇[20(S)-PPD]表观油水分配系数,并研究其在体肠吸收机理。方法利用高效液相色谱法测定20(S)-PPD浓度,采用摇瓶法测定其表观油水分配系数。采用大鼠在体单向肠灌流实验,按重量法计算动力学参数。结果 37℃条件下,20(S)-PPD在正辛醇饱和水相中的表观油水分配系数为(1og Papp=1.72),在不同pH磷酸盐缓冲液中的表观油水分配系数与水相中数值接近。20(S)-PPD在整个肠段都有吸收,吸收速率常数按大小依次为十二指肠、空肠、回肠、结肠,结肠段的Ka和Papp与其他肠段比较相对较小,说明20(S)-PPD的主要吸收部位在小肠。结论不同pH值的介质对20(S)-PPD表观油水分配系数影响不大;20(S)-PPD在整个肠段均有良好的吸收,小肠为主要吸收部位。在该药物开发方面,应设法延长其在小肠内的滞留时间,以提高生物利用度。

Objective To determine the apparent oil/water partition coefficient of 20（S）-PPD and to investigate its absorption mechanism by in situ perfusion method in rat intestines. Methods The concentration of 20（S）-PPD was determined by HPLC. A shake flask method was established to determine oil/water partition coefficient of 20（SI-PPD. In situ perfused rat intestinal model was used to calculate the kinetic parameters by weight methods. Results At 37 ~C, the log Papp of 20（S）-PPD in octanol/water system was 1.72. Log Papp in different phosphate buffer solutions were close to that in aqueous phase. 20（S）-PPD was well absorbed in general intestinal tract, where its absorption rate constant （K~） was duodenum^jejunum^ileum〉colon. K~ and Papp in rat colon was relatively lower than in other intestinal tracts. It implied that the main absorption segment of 20（S）-PPD was small intestine. Conclusion The pH of buffer solution had no influence on its distribution coefficient. 20（S）-PPD was well absorbed in general intestinal tract with small intestine as its main absorption segment. It suggested that its stay in small intestine should be prolonged to promote its bioavailability in the relevant new-drug development.