碳酸钙-2
化学
体内
肠道通透性
牛磺胆酸
磁导率
亲脂性
药品
并行传输
紧密连接
色谱法
白蛋白
体外
吸收(声学)
生物利用度
药理学
势垒函数
P-糖蛋白
跨细胞
肠上皮
流出
生物物理学
生物化学
胆汁酸
膜
生物
材料科学
复合材料
生物技术
作者
Shinji Yamashita,Tomoyuki Furubayashi,Makoto Kataoka,Toshiyasu Sakane,Hitoshi Sezaki,Hideaki Tokuda
标识
DOI:10.1016/s0928-0987(00)00076-2
摘要
The effects of various experimental conditions on in vitro drug permeability to Caco-2 monolayers were investigated to determine the optimized conditions for the prediction of intestinal drug absorption. Concerning the pH of the transport medium in the Caco-2 study, two different pH values, 6.0 and 7.4, were tested for the apical medium with the pH of the basolateral medium fixed to 7.4. The change in the apical pH showed pronounced effects on the permeability of both passively and actively transported drugs. It was found that the transport study under the condition of an apical pH value of 6.0 showed a better prediction of in vivo drug absorption in human. The appropriate conditions for determining the permeability of poorly soluble drugs were also examined. First, the effects of bile acids, surfactant and some agents used for solubilizing drugs on the permeability and transepithelial electrical resistance (TEER) of Caco-2 monolayers were investigated. Taurocholic and cholic acid showed no effects on the permeability of 3H-Dexamethasone (DEX) and TEER at 10 mM concentration, suggesting the possibility of use in the Caco-2 study. Polyethyleneglycol-400 and dimethylsulfoxide reduced the permeability of DEX concentration dependently, whereas ethanol induced no significant changes in the permeability. Furthermore, it was demonstrated that the addition of plasma protein (bovine serum albumin) to the basolateral medium apparently facilitated the transport of poorly soluble drugs with high lipophilicity across Caco-2 monolayers. These findings clearly suggest the importance of considering the physiological conditions of in vivo drug absorption in optimizing the in vitro experimental conditions for transport study using Caco-2 cells, in order to obtain a satisfactory in vitro-in vivo correlation.
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