周伟 狄留庆 毕肖林 陈乐天 杜秋. 在体肠循环法研究连翘酯苷A的肠吸收机制J. 药学学报, 2010,45(11): 1373-1378.
引用本文: 周伟 狄留庆 毕肖林 陈乐天 杜秋. 在体肠循环法研究连翘酯苷A的肠吸收机制J. 药学学报, 2010,45(11): 1373-1378.
ZHOU Wei, DI Liu-Qiang, BI Xiao-Lin, CHEN Le-Tian, DU Qiu. Intestinal absorption of forsythoside A by rat circulation in situJ. 药学学报, 2010,45(11): 1373-1378.
Citation: ZHOU Wei, DI Liu-Qiang, BI Xiao-Lin, CHEN Le-Tian, DU Qiu. Intestinal absorption of forsythoside A by rat circulation in situJ. 药学学报, 2010,45(11): 1373-1378.

在体肠循环法研究连翘酯苷A的肠吸收机制

Intestinal absorption of forsythoside A by rat circulation in situ

  • 摘要:

    考察药物浓度、不同肠段、pH、细胞旁路以及代谢酶 (CYP3A) 和转运体 (P-gpMRP2SGLT1) 的底物、抑制剂对连翘酯苷A吸收的影响。以酚红为标示物, 采用大鼠在体肠循环法研究不同浓度 (2.65.210.4 μg·mL−1) 的连翘酯苷A在大鼠各肠段的吸收情况。结果表明, 不同浓度的连翘酯苷A在大鼠肠道吸收无显著性差异 (P > 0.05); 其在十二指肠、空肠、回肠、结肠段的吸收未发生明显变化。由此可推测在实验浓度范围内, 连翘酯苷A在大鼠肠道内的吸收可能为被动扩散, 且无特定的吸收部位。在大鼠肠循环液中加入4 μg·mL−1环孢素、50 μmol·L−1咪达唑仑后, 循环液中连翘酯苷A的剩余药量分别为466.160463.429 μg, 与对照组相   比均有不同程度的增加 (P < 0.05), 且随着环孢素、咪达唑仑浓度的增加, 循环液中的剩余药量呈增加趋势; 加入50 μmol·L−1地高辛、10 μg·mL−1 EDTA, 循环液中连翘酯苷A的剩余药量分别为325.110369.888 μg, 与对照组相比均有不同程度的降低 (P < 0.05), 且随着地高辛、EDTA浓度的增加, 循环液中的剩余药量呈降低趋势; 而不同浓度的甘露醇对循环液中连翘酯苷A的剩余药量几乎无影响。由此推断, 连翘酯苷A在大鼠肠道的吸收以被动扩散为主, 同时存在细胞旁路转运, P-gpCYP3A酶的底物对连翘酯苷A的吸收呈剂量依赖性的影响。

     

    Abstract:

    This study is to investigate the effects of concentration, intestinal section, pH, paracellular route, substrate/inhibitor of enzyme (CYP3A) and proteins (P-gp, MRP2, SGLT1) on the absorption of forsythoside A.  The absorption of three concentrations (2.6, 5.2, and 10.4 μg·mL−1) of forsythoside A in different intestinal  segments was studied with phenol red as the marker by rat circulation in situ.  The results showed that the  residue of forsythoside A with different concentrations had little significant difference from that obtained after perfusing via duodenum, jejunum, ileum and colon, which indicated that the absorption of forsythoside A was passive diffusion and had no difference in different segments of rat intestine.  The residue of forsythoside A  increased to 466.160 and 463.429 μg respectively when cyclosporine (4 μg·mL−1) or midazolam (50 μmol·L−1) was added to the circulation fluid, which showed significant difference compared to the control group (P < 0.05).  Moreover, the residue of forsythoside A showed a tendency of increase with the increase of cyclosporine or  midazolam.  When digoxin (50 μmol·L−1) or EDTA (10 μg·mL−1) was added to the circulation fluid, the residue of forsythoside A decreased to 325.110 and 369.888 μg respectively, which showed significant differenceas compared to the control group (P < 0.05).  Besides, the residue of forsythoside A showed a tendency of reduction with the increase of digoxin or EDTA.  However, there is no significant change in the absorption of forsythoside A when the different concentrations of mannitol were added to the circulation fluid.  The results above indicated that the absorption of forsythoside A was mainly passive diffusion and involved paracellular route at the same time.  In addition, the substrates of P-gp or CYP3A had dose-dependent effect on the absorption of forsythoside A.

     

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