中国临床药学杂志2012，Vol.21Issue(3)：133-137,5.
抗肿瘤药物西美替尼在Caco-2细胞模型中的吸收转运
Absorption and transportation of anti-cancer drug cimetinib across Caco-2 monolayer model
摘要
Abstract
AIM To study the absorption and transportation of anti-cancer drug cimetinib using Caco-2 monokyer model. METHODS A highly sensitive HPLC analytic method for cimetinib determination was developed, and the specificity and precision were evaluated. The Caco-2 cell model was established and used to study the transportation of cimetinib. The concentration of cimetinib in transportation medium was measured by HPLC, and the apparent permeability coefficients (Papp) were calculated. RESULTS The developed HPLC analytic method had good specificity and precision. There was no significant concentration dependence in the transportation process of cimetinib. The transportation rate increased with the concentration of cimetinib at the low concentration, and the transportation reached to saturation at the high concentration. The Papp values of various concentration of cimetinib (3.91×10-5, 3.29×10-5, 1.90×10-5 and 0.95×10-5cm·s-1) almost were higher than the critical Papp value of poor absorption drugs (1×10-5cm·s-1). The transportation of cimetinib across Caco-2 cell monolayers was highly directional. The Papp values of cimetinib from apical side to basolateral side (AP→BL) was significantly higher than those of basolateral side to apical side (BL→AP) with the ratio range from 2.36 to 7.58. Sodium azide, an ATP inhibitor, remarkably decreased transportation of cimetinib from AP→BL direction, and increased the transportation from BL→AP, which suggested that the transportation of cimetinib was energy-dependent. The Papp values of cimetinib from AP→BL direction was significantly decreased in the presence of glucose. CONCLUSION The results suggest that cimetinib is mainly actively absorbed by a transporter-mediated process. Cimetinib shows good intestinal absorption, and could be formulated in oral administration dosages.关键词
抗肿瘤药物/西美替尼/Caco-2细胞单层模型/表观渗透系数/吸收/转运Key words
anti-cancer drug/ cimetinib/ Caco-2 cell monolayer model/ apparent permeability coefficient/absorption/ transportation引用本文复制引用
张建明,任筱青,沙先谊,方晓玲..抗肿瘤药物西美替尼在Caco-2细胞模型中的吸收转运[J].中国临床药学杂志,2012,21(3):133-137,5.基金项目
国家"重大新药创制"科技重大专项(编号:2009ZX09103-084) （编号:2009ZX09103-084）
