论文部分内容阅读
目的研究抗肿瘤药物西美替尼在Caco-2细胞模型中的吸收转运。方法建立Caco-2细胞转运模型,采用HPLC法测定药物浓度,计算表观渗透系数(P_(app)),研究西美替尼的Caco-2细胞跨膜转运情况。结果西美替尼在转运过程中没有明显的浓度依赖性。在低浓度范围内,药物的转运速率随着浓度的增加而增加;在较高浓度时达到饱和。西美替尼不同浓度的P_(app)值(3.91×10~(-5)、3.29×10~(-5)、1.90×10~(-5)和0.95×10~(-5)cm·s~(-1))基本都大于难吸收药物的临界值(1×10~(-5)cm·s~(-1))。西美替尼在Caco-2细胞中的转运呈现较强的方向性,从肠腔面到基底面的P_(app)值显著大于从基底面到肠腔面的P_(app)值(2.36～7.58倍)。ATP抑制剂叠氮化钠能显著降低西美替尼的正向转运程度,并升高其反向转运程度。当加入葡萄糖后,从肠腔面到基底面的跨膜转运程度显著降低。结论西美替尼主要是以转运载体介导的主动转运方式被吸收,其小肠吸收情况较好。
Objective To study the absorption and transport of anti-tumor drug cimetidin in Caco-2 cell model. Methods The Caco-2 cell transport model was established. The drug concentration was determined by HPLC, and the apparent permeability coefficient (P app) was calculated to study the transmembrane transport of Cime-2 cells. Results There was no significant concentration dependence of cimetidine during transport. At low concentrations, the drug transport rate increased with increasing concentration; saturation occurred at higher concentrations. The values of p_ (app) for salmeterin at different concentrations were 3.91 × 10 ~ (-5), 3.29 × 10 ~ (-5), 1.90 × 10 ~ (-5) and 0.95 × 10 ~ (-5) cm · s ~ (-1)) were all larger than the critical value of difficult to absorb drugs (1 × 10 -5 cm · s -1). The migration of cimetidine in Caco-2 cells showed a strong direction, and the value of P app from the luminal surface to basal plane was significantly greater than the value of app from basal plane to gut lumen (2.36 ~ 7.58 times). Sodium azide, an ATP inhibitor, significantly reduced the positive transport of cimetidine and increased its reverse transport. When glucose was added, the transmembrane transport from the luminal surface to the basal surface was significantly reduced. Conclusion Simitinib is mainly absorbed by transporter-mediated active transport and its intestinal absorption is better.