单向灌流法研究磷酸川芎嗪的大鼠在体肠吸收

Studies on the intestinal absorption of tetramethylpyrazine phosphate in rats by single pass intestinal perfusion method

目的研究磷酸川芎嗪的大鼠在体肠吸收性质。方法运用单向灌流模型、采用HPLC法对药物的质量浓度进行检测,分别研究灌流速度、药物质量浓度、pH值以及吸收部位对磷酸川芎嗪吸收的影响。结果灌流速度和pH值对磷酸川芎嗪的吸收速率常数(ka)和表观吸收系数(Papp)有显著性影响;药物质量浓度对ka和Papp无显著性影响;小肠各段间药物吸收的ka和Papp无显著性差异,但与回肠段相比吸收明显增大。结论磷酸川芎嗪的吸收速率不受药物质量浓度的影响,而与灌流速度、灌流液的pH值和肠段部位有关。药物在全肠道吸收较好,吸收窗主要在小肠,且小肠内无明显的特定吸收部位。

Objective To investigate the absorption characteristic of tetramethylpyrazine phosphate （TMPP） in various intestinal segments. Methods TMPP concentration in rat intestinal perfusion solution was determined by HPLC. Rat single pass intestinal perfusion method （SPIP） was employed to investigate the effects of flow rate, pH of perfusion solution and testinal segments on drug＇s absorption rate constant （ka） and the intestinal apparent permeation coefficients （Papp）. Results The values of the ka and the Papp were significantly affected by the flow rate and pH of perfusion solution and were not significantly affected by the concentration of perfusion solution. In different small intestinal segments, ka and Papp had no obviously difference, but were higher significantly compared with that in colon. Conclusions The absorption rate of TMPP is not affected by drug concentration but is obviously affected by the flow rate, pH of regurgitation fluid and intestinal segments. TMPP is well absorbed at all segments of intestine in rats where there is no special absorption site.