阿立哌唑在Caco-2细胞单层模型中的跨膜转运(英文)  

Transport of aripiprazole across Caco-2 monolayer model

作　　者：吴娟[1] 沙先谊[1] 方晓玲[1] 

机构地区：[1]复旦大学药学院,上海200032

出　　处：《药学学报》2009年第2期188-191,共4页Acta Pharmaceutica Sinica

摘　　要：本文研究了阿立哌唑(aripiprazole)在Caco-2细胞模型中的跨膜转运特征。一种体外培养的人小肠上皮细胞模型——Caco-2细胞模型应用于阿立哌唑的跨膜转运研究。评价了时间、供给液浓度、pH值、温度及P-糖蛋白抑制剂对阿立哌唑跨膜转运的影响。采用高效液相色谱法检测药物浓度。结果表明阿立哌唑主要通过被动扩散的机制转运,同时兼有载体介导转运。阿立哌唑的转运量与时间、pH值、温度成正相关。表观渗透系数Papp值随供给液浓度升高而增大,10μg·mL-1时趋向饱和,之后随阿立哌唑浓度的增加而逐渐减小。P-糖蛋白抑制剂环孢菌素-A显著增加阿立哌唑的跨膜转运。This study aimed to investigate the transport characteristics of aripiprazole. A human intestinal epithelial cell model Caco-2 cell in vitro cultured had been applied to study the transport of aripiprazole. The effects of time, concentration of donor solutions, pH, temperature and P-glycoprotein inhibitor on the transport of aripiprazole were investigated. The determination of aripiprazole was performed by HPLC. It is concluded that aripiprazole is transported through the intestinal mucosa via a passive diffusion mechanism primarily, coexisting with a carrier-mediated transport. The transport of aripiprazole is positively correlated to transport time, pH, and temperature. Papp increased with donor concentrations up to 10 μg·mL^-1, and then decreased for higher concentrations. The P-glycoprotein inhibitor cyclosporine A significantly enhanced the transport amount of aripiprazole.

关 键 词：阿立哌唑 CACO-2细胞 转运 P-糖蛋白 

分 类 号：R964[医药卫生—药理学]