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目的 :研究 AG337在 Caco- 2细胞模型中的转运机制。方法 :改变药物浓度和实验温度以及使用合适抑制剂 ,测定AG337的跨细胞转运速率及其在细胞内的累积量。结果 :AG337的跨细胞转运显示强烈的有向性 ,B→ A转运 (细胞绒毛面Apical→基底面 Basolateral)大于 A→ B10倍以上 ,P-糖蛋白的专属抑制剂维拉帕米 ( Ver)可以消除这种有向性 ;温度从 37℃至 4℃时 B→ A的转运速率下降 5 0倍 ,而 A→ B下降不大。结论 :AG337在 Caco- 2模型中的跨细胞转运 ,受到 P-糖蛋白强烈的外排作用
OBJECTIVE: To study the transport mechanism of AG337 in Caco-2 cell model. METHODS: The transcytosis rate of AG337 and its intracellular accumulation were measured by varying the drug concentration and the experimental temperature and using appropriate inhibitors. RESULTS: The transcellular transport of AG337 showed a strong directivity. B → A transport (Apical → Basolateral) was greater than that of A → B, and the inhibitor of P-glycoprotein, verapamil (Ver) Can eliminate this kind of directivity; The transfer rate of B → A drops 50 times while the temperature changes from 37 ℃ to 4 ℃, while the A → B does not decrease greatly. CONCLUSION: Transcellular transport of AG337 in the Caco-2 model is strongly effluxed by P-glycoprotein