生物等效性和生物利用度杂志

抽象的

P-gp Induction by Curcumin: An Effective Antidotal Pathway

He Juan, Tang Jing, Yang Wan-Hua, Song Juan, Liu Xiao-Lei and Peng Wen-Xing

Aim: We had reported that low dose curcumin could reduce the absorption of talinolol. The investigation in this study provided more information about inductive effect of high dose curcumin and further elucidated the mechanism between curcumin and drug interactions mediated by intestinal p-gp. Methods: The pharmacokinetics of talinolol after high dose curcumin was studied in 12 healthy volunteers using HPLC-MS/ESI method. The function, expression and mRNA levels of p-gp were determined in p-gp over-expressing caco-2 cells by flowcytometry or real-time quantitative polymerase chain reaction. Results: High dose curcumin decreased the AUC0-∞ and Cmax of talinolol by 42% and 29%, respectively, CL/F was significantly increased by approximately 77% versus control. In vitro studies, curcumin and its metabolite tetrahydrocurcumin significantly upregulated function, expression and MDR1 mRNA levels of p-gp in a concentrationand time-dependent manner, with significant results observed as soon as 1 h after incubation. The remarkable increases in p-gp expression were not accompanied by proportional increases in p-gp transport activity. Conclusions: Simultaneous administration of curcumin might alter the pharmacokinetics of co-administrated drugs by p-gp induction, by which curcumin may confer protection from endogenous and exogenous toxins