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-gp、MRP2和SGLT1)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(2.6、5.2和10.4μg.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4μg.mL?1环孢素、50μmol.L?1咪达唑仑后,循环液中连翘酯苷A的剩余药量分别为466.160和463.429μg,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50μmol.L?1地高辛、10μg.mL?1 EDTA后,循环液中连翘酯苷A的剩余药量分别为325.110和369.888μg,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,且P-gp及CYP3A酶的底物对连翘酯苷A的吸收呈剂量依赖性的影响。
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.
出处
《药学学报》
CAS
CSCD
北大核心
2010年第11期1373-1378,共6页
Acta Pharmaceutica Sinica
基金
江苏省中医药局项目(HZ07051)
江苏省"青蓝工程"科技创新团队支持计划[苏教师(2008)30号]83271038
E-mail:diliuqing928@163.com
关键词
连翘酯苷A
在体肠循环法
吸收机制
forsythoside A
rat circulation in situ
absorption mechanism
