雷公藤甲素大鼠在体肠吸收特性研究

目的考察雷公藤甲素在大鼠肠道的吸收情况,为其安全合理应用提供生物药剂学依据。方法采用大鼠在体肠灌流实验,利用超高效液相色谱(UPLC)法测定雷公藤甲素的量,分别研究吸收部位和药物浓度对雷公藤甲素吸收的影响。结果4、8.3、20μmol/L雷公藤甲素灌流液在各肠段的有效渗透系数(Peff*)和10 cm肠段吸收百分比(10 cm%ABS)依次为十二指肠>结肠>空肠>回肠,各肠段之间无显著性差异(P>0.05)。不同质量浓度(4~20μmol/L)的雷公藤甲素在肠道内的吸收无显著性差异(P>0.05)。结论雷公藤甲素在大鼠肠道内有较好的肠吸收,对肠段无明显的吸收部位选择性,一定范围内的药物浓度对雷公藤甲素的Peff*和10 cm%ABS无影响,初步判断其吸收机制为被动扩散。

Studies on rat intestinal absorption of triptolide in situ

Objective To investigate the rat intestinal absorption behavior of triptolide and provide the biopharmaceutic basis for reasonable application. Methods The intestinal absorption of triptolide was detected by the in situ single pass intestine perfusion method. The content of triptolide in the perfusate was determined by UPLC. Results The effective permeability coefficients (P_(eff)~*) and absorption percentage of 10 cm intestinal segments (10 cm% ABS) of triptolide had no significant difference (P>0. 05) at concentration of 4, 8. 3, and 20μmol/L in four different regions of intestine of rat, which showed duodenum> colon>jejunum>ileum. The P_(eff) and 10 cm% ABS of triptolide had no significant difference (P>0. 05) among the concentration ranges of 4-20μmol/L. Conclusion Triptolide could be well absorbed in general intestinal tract without specific absorption site. The concentration of triptolide has no influence on its Pe_ (eff)~* and 10 cm% ABS in the certain range, which preliminarily judges that triptolide is absorbed by passive diffusion mechanism.