左氧氟沙星在人胃黏膜上皮细胞中的摄取特征

Study on the uptake of levofloxacin by gastric epithelial system cells

目的：研究左氧氟沙星在人胃黏膜上皮细胞（GES-1）中的摄取特征。方法 GES-1细胞与左氧氟沙星孵育后用高效液相色谱法和考马斯亮蓝法研究其在细胞内的药物摄取量，同时考察时间、药物浓度、温度、pH值和转运体抑制剂（环孢素A、维拉帕米和西咪替丁）对左氧氟沙星在GES-1细胞中摄取的影响。结果在GES-1细胞内，左氧氟沙星摄取量，在1～5 min明显增加，在7.5～15.0 min缓慢增加并达到稳态；摄取量随着细胞外左氧氟沙星浓度的增加而增加，但不呈线性增加。在37℃、pH 7.4时，摄取量最大。环孢素A和维拉帕米能增加细胞内药物摄取量，分别较对照组增加了2.81％～13.23％，2.07％～10.28％，但差异无统计学意义（ P＞0.05）；西咪替丁对此均无影响。结论左氧氟沙星经转运蛋白的介导方式进入细胞内，P-糖蛋白可能参与了左氧氟沙星在GES-1细胞中的摄取过程。

Objective To investigate the uptake mechanisms of levoflox-acin by gastric epithelial system （ GES-1 ） cells.Methods The uptake of levofloxacin in GES-1 cells were determined by HPLC and coomassie brilliant blue.The influences of incubated time ,extracellular levofloxacin concentrations, pH, temperature, inhibitors of transporters on the uptake of levofloxacin by GES -1 cells were tested.Results The uptake of levofloxacin by GES-1 cells was increased sharply at 1-5 minutes then was increased moderately at 7.5 -15.0 minutes and reached a steady state after the start of the incubation.The accumulation of levofloxacin increased with the extracellar levels ,but which was not linearly.The up-take of levofloxacin reached a maximum when temperature was 37 ℃and pH was 7.4.The increase in levofloxacin accumulation by cyclosporin A and verapamil in GES -1 cells was by 2.81% -13.23%, 2.07% -10.28%, respectively （ P 〉0.05 ）.Effect of the cimetidine was not same that the two drugs.Conclusion Levofloxacin enters into GES -1 cells in carrier-mediated transport manner.P-gp might be involved in the process of uptake of levofloxacin in GES -1 cells.