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为了研究冰片对磷酸川芎嗪的肠吸收以及考察冰片对大鼠灌胃磷酸川芎嗪后药代动力学的影响,初步探讨冰片促吸收的机制,本文采用在体肠循环实验研究不同浓度的冰片对磷酸川芎嗪在十二指肠、空肠、回肠及结肠等4个肠段吸收的影响。通过大鼠分别灌胃磷酸川芎嗪、磷酸川芎嗪与冰片的混合物及磷酸川芎嗪与维拉帕米的混合物,采用高效液相色谱法测定不同时间血浆中磷酸川芎嗪的浓度,比较3组整体动物实验的药代动力学参数。结果表明磷酸川芎嗪在4个肠段的单位面积吸收量顺序为:结肠>十二指肠>空肠>回肠,且随药物浓度的增大各个肠段的单位面积吸收量均没有吸收饱和现象,推断磷酸川芎嗪在大鼠肠道以被动扩散方式吸收。加入冰片后,磷酸川芎嗪在4个肠道的单位面积吸收量均增加。冰片质量浓度为10μg·mL-1时,与对照组相比,无显著性差异(P>0.05);而冰片质量浓度为25和50μg·mL-1时,与对照组相比,均具有显著性差异(P<0.05),可见冰片对磷酸川芎嗪的促吸收无明显的靶部位,但其发挥促吸收作用需要一定的浓度。整体动物实验结果表明,冰片和维拉帕米均提高了磷酸川芎嗪的生物利用度,冰片促进磷酸川芎嗪生物利用度增加的机制之一可能是由于抑制了肠上皮细胞CYP3A代谢和P-gp的外排作用。
In order to study the intestinal absorption of borneol on tetramethylpyrazine phosphate and to investigate the effect of borneol on the pharmacokinetics of ligustrazine phosphate in rats, the mechanism of promoting absorption of borneol was preliminarily studied. In this study, Tetramethylpyrazine phosphate in the duodenum, jejunum, ileum and colon absorption of the four intestines. The rats were respectively gavaged with a mixture of ligustrazine phosphate, ligustrazine phosphate and borneol and a mixture of ligustrazine and verapamil. Plasma concentrations of ligustrazine in different time groups were determined by HPLC. Pharmacokinetic parameters of animal experiments. The results showed that the order of absorption of ligustrazine phosphate per unit area in four intestine segments was: colon> duodenum> jejunum> ileum. With the increase of drug concentration, there was no absorption saturation per unit area of intestinal segments, Inferred that ligustrazine phosphate in the intestine of rats is absorbed by passive diffusion. After adding borneol, tetramethylphosphate phosphate in four intestinal per unit area increased. Compared with the control group, no significant difference was found between borneol concentration of 10μg · mL-1 and control group (P> 0.05), while borneol concentration of 25 and 50μg · mL-1 had significant difference compared with the control group (P <0.05). It can be seen that borneol has no obvious target site for promoting the absorption of ligustrazine phosphate, but it needs a certain concentration to promote absorption. The overall animal experimental results show that both borneol and verapamil improve the bioavailability of ligustrazine phosphate and one of the mechanisms by which borneol increases the bioavailability of ligustrazine phosphate may be due to inhibition of CYP3A metabolism and P-gp The role of efflux.