5-羟基雷公藤内酯醇不是P-糖蛋白底物或抑制剂  

5-hydroxytriptolide is neither a substrate nor an inhibitor of P-glycoprotein

作　　者：徐佳[1] 向志雄[1] 刘海燕[1] 

机构地区：[1]上海医药集团股份有限公司中央研究院,上海201203

出　　处：《上海医药》2013年第13期56-61,共6页Shanghai Medical & Pharmaceutical Journal

基　　金：国家新药创制重大专项(2009ZX09102)

摘　　要：目的:评价5-羟基雷公藤内酯醇(T8)是否是依赖P-糖蛋白(P-glycoprotein,P-gp)介导的底物或抑制剂,从而评价T8在临床上和其他药物(P-糖蛋白的底物或抑制剂)合用时发生药物-药物相互作用的可能性,为临床药物相互作用研究提供参考。方法:采用MDCK-MDR1细胞模型,测定T8(1μmol/L)的校正外排比(corrected efflux ratio,CER)和以罗丹明123(Rhodamine123,Rho123)和紫杉醇为底物时1μmol/L和5μmol/L的T8对P-gp的抑制率。结果:T8的校正外排比为1.07,T8对P-gp的抑制率均接近0。结论:T8不是P-gp的潜在底物和抑制剂,因此T8和P-gp的底物和抑制剂发生药物-药物相互作用的可能性很低。Objective： To evaluate whether 5-hydroxytriptolide （T8） is a substrate or an inhibitor of P-glycoprotein （P-gp）, and its potential of drug-drug interaction with P-gp substrates or inhibitors in clinic, which can provide a reference for clinical drug-drug interaction study. Methods： MDCK-MDR1 cell in vitro was used throughout the experiment to determine the corrected efflux ratio ofT8 at 1 μmol/L and the inhibition rate ofT8 at 1 μmol/L and 5μmol/L when rhodamine123 and paclitaxel were used as substrates. Results： The corrected efflux rate and the inhibition rate of T8 are 1.07 and nearly 0, respectively. Conclusion： T8 is neither a substrate nor an inhibitor of P-gp, and its potential of drug-drug interaction with P-gp substrates or inhibitors is very low.

关 键 词：5-羟基雷公藤内酯醇 MDCK-MDR1 P-糖蛋白 

分 类 号：R961[医药卫生—药理学] R969.2[医药卫生—药学]