Hilgers A R, Conradi R A, Burton P S
Drug Delivery Systems Research, Upjohn Company, Kalamazoo, Michigan 49001.
Pharm Res. 1990 Sep;7(9):902-10. doi: 10.1023/a:1015937605100.
Human colon adenocarcinoma (Caco-2) cells, when grown on semipermeable filters, spontaneously differentiate in culture to form confluent monolayers which both structurally and functionally resemble the small intestinal epithelium. Because of this property they show promise as a simple, in vitro model for the study of drug absorption and metabolism during absorption in the intestinal mucosa. In the present study, the transport of several model solutes across Caco-2 cell monolayers grown in the Transwell diffusion cell system was examined. Maximum transport rates were found for the actively transported substance glucose and the lipophilic solutes testosterone and salicyclic acid. Slower rates were observed for urea, hippurate, and saliylate anions and were correlated with the apparent partition coefficient of the solute. These results are similar to what is found with the same compounds in other, in vivo absorption model systems. It is concluded that the Caco-2 cell system may give useful predictions concerning the oral absorption potential of new drug substances.
人结肠腺癌（Caco-2）细胞在半透膜滤器上生长时，在培养过程中会自发分化形成汇合的单层细胞，其结构和功能均类似于小肠上皮。由于这一特性，它们有望成为研究药物在肠黏膜吸收过程中的吸收和代谢的简单体外模型。在本研究中，检测了几种模型溶质在Transwell扩散池系统中生长的Caco-2细胞单层上的转运情况。发现主动转运物质葡萄糖以及亲脂性溶质睾酮和水杨酸的最大转运速率。尿素、马尿酸盐和水杨酸盐阴离子的转运速率较慢，且与溶质的表观分配系数相关。这些结果与在其他体内吸收模型系统中对相同化合物的研究结果相似。结论是，Caco-2细胞系统可能对新药物质的口服吸收潜力做出有用的预测。
