洋川芎内酯Ⅰ大鼠在体肠吸收动力学研究

In situ Intestinal Absorption Kinetics of Senkyunolide Ⅰ in Rats

目的研究洋川芎内酯I大鼠在体肠吸收特性。方法运用大鼠在体单向灌流技术考察洋川芎内酯Ⅰ在大鼠4个肠段的吸收动力学特征;采用高效液相色谱法(HPLC)测定灌流液中洋川芎内酯I的含量;从药物质量浓度、吸收部位、灌流介质3个方面对洋川芎内酯I的各肠段吸收特性进行考察;利用重量法计算动力学参数。结果不同质量浓度(514、257和128.5μg.mL-1)洋川芎内酯Ⅰ在相同肠段的吸收速率常数ka和表观吸收系数Papp均无显著性差异(P>0.05);十二指肠段的表观吸收系数Papp与空肠、回肠和结肠均有极显著性差异(P<0.001),而空肠、回肠、结肠间均无显著性差异。结论洋川芎内酯I在大鼠肠道的吸收在所选剂量范围内呈线性动力学过程,提示其吸收可能以被动转运为主;在大鼠各肠段均有较好吸收,其中十二指肠为其最佳吸收部位。

OBJECTIVE To study the in situ intestinal absorption kinetics of senkyunolide I in rats. METHODS The absorption of senkyunolide I in four segments of rat intestine was investigated using the in situ single-pass perfusion method, and the drug content was measured by HPLC. The absorption kinetics of senkyunolide I at different segments of intestine, drug concentration, and perfusion medium were studied. RESULTS Drug concentration had no significant influence on the ka and the P app, values of senkyunolide I （P 〉 0. 05 ） in the range of 128.5 -514 μg mL-1. Papp values of senkyunolide I at duodenum were significantly higher than those at the other three regions of intestine （ P 〈 0. 001 ）. But no significant differences in the Papp value （ P 〉 0. 05 ） were found among jeju- num, ileum, and colon. CONCLUSION The absorption of senkyunolide I complied with linear kinetics in the dose range studied, indicating that its absorption may be mediated mainly by passive transport. Senkyunolide I could be absorbed at all the studied intesti- nal segments while duodenum seemed to be the best absorption segment for it.