丁香苦苷大鼠在体肠吸收动力学研究

目的:研究中药单体丁香苦苷的在体肠吸收机制。方法:运用单向灌流模型、采用HPLC对药物的质量浓度进行检测,分别研究吸收部位、药物质量浓度、pH以P-糖蛋白抑制剂对丁香苦苷吸收的影响。结果:丁香苦苷在十二指肠、空肠、回肠、结肠的吸收速率常数分别为0.002 55,0.006 30,0.009 00,0.007 99 min-1;不同的药物质量浓度0.090,0.180,0.360g·L-1在小肠的吸收速率常数分别为0.003 70,0.007 08,0.006 94 min-1;不同的pH 7.4,6.8,5.0时在小肠的吸收速率常数分别为0.007 33,0.007 47,0.003 62 min-1。P-糖蛋白抑制剂对丁香苦苷肠吸收具有显著性影响(P<0.05)。结论:丁香苦苷在肠道下部吸收较好;药物浓度低时,吸收速率常数小,中、高浓度时,吸收速率常数增大;在pH 5.0～7.4,pH 5.0吸收速率常数较小,pH 6.8,7.4吸收速率常数增大,丁香苦苷为P-糖蛋白底物。

Study on intestinal absorption kinetics of syringopicroside in rats

Objective: To study the intestinal absorption mechanism of traditional Chinese medicine monomer syringopicroside in rats. Method: The in situ rat single-pass intestinal perfusion model was established to detect the concentration of syringopicroside by HPLC. The absorption at different intestine segments in rat and the influence of concentration, pH and P-glycoprotein inhibitors of the drug solution on the absorption of syringopicroside were also observed. Result: The absorption rate constant (K_a) of syringopicroside at duodenum, jejunum, ileum, and colon were 0.002 55, 0.006 30, 0.009 00, 0.007 99 min^-1, respectively; K_a from intestine at syringopicroside concentration of 0.090, 0.180, 0.360 g·L^-1were 0.003 70, 0.007 08, 0.006 94 min^-1, respectively; and K_a at pH of 7.4, 6.8 and 5.0 were 0.007 33, 0.007 47, 0.003 62 min^-1, respectively. P-glycoprotein inhibitor on the intestinal absorption of syringopicroside showed significant influence (P<0.05). Conclusion: Syringopicroside is well absorbed at the lower small intestine. When the drug concentration is low, the absorption rate constant is low, where as K_a increases at medium and high concentrations; the K_a is low at pH 5.0 and increases at pH 6.8 and pH 7.4. Syringopicroside is proved to be a substrate of P-glycoprotein.