一种新的小檗碱衍生物CPU-86017在人小肠上歧细胞（Caco-2细胞）中的转运与摄取特性  

作　　者：杨海涛 王广基 

机构地区：[1]CenterofPharmacokinetics,ChinaPharmaceuticalUniversity,Nanjing210009,China

出　　处：《Acta Pharmacologica Sinica》2003年第12期1185-1191,共7页中国药理学报（英文版）

摘　　要：AIM: The characteristics of transepithelial transport and uptake of CPU-86017 {[7-(4-chlorbenzyl)-7,8,13,13α-tetrahydroberberine chloride, CTHB]}, a new antiarrhythmia agent and a new derivative of berberine, were investigated on epithelial cell line (Caco-2) to further understand the absorption mechanism of berberine and its derivatives.METHODS: Caco-2 cell was used. RESULTS: 1) The permeability coefficient from the apical (AP) to basolateral(BL) of CPU-86017 was approximately 5 times higher than that from BL-to-AP transport. The effects of a P-glycoprotein (P-gp) inhibitor-cyclosporin A, some surfactants, and lower pH on the transepithelial transport of CPU-86017 were also observed. Cyclosporine A at 7.5 mg/L had no effect on the transepithelial electrical resistance(TEER); an about 4-fold enhancement on the transepithlial transport of CPU-86017 was observed. Some surfactants (sodium citrate, sodium deoxycholate, and sodium dodecyl sulfate) at 100 μmol/L and low pH (pH=6.0) induced a reversible decrease of TEER; enhancements of the transepithelial transport of CPU-86017 were also observed with some surfactants; 2) In the process of uptake of CPU-86017, the initial uptake rates of CPU-86017 were saturable with a Vmax of (250±39)μg·min^-1·g^-1 (protein) and Km of (0.90±0.12) mmol/L. This process was enhanced by cyclosporine A (7.5 mg/L) with a Vmax of (588±49)μg·min^-1·g^-1(protein) and Km (0.42±0.08)mmol/L.CONCLUSION: Some surfactants and P-gp inhibitors can be considered as enhancers of its transepithelial transport and uptake.

关 键 词：小檗碱衍生物 CPU-86017 小肠上歧细胞 CACO-2细胞 细胞转运 

分 类 号：R965[医药卫生—药理学]