茶多酚对兰索拉唑及其代谢产物在大鼠体内药动学的影响

目的:研究茶多酚对兰索拉唑及其代谢产物5-羟基兰索拉唑和兰索拉唑砜在大鼠体内药动学的影响.方法:16只SD雄性大鼠随机分为单独用药组和联合用药组,前14 d联合用药组灌胃给予茶多酚400 mg·kg-1,单独用药组灌胃给予等体积生理盐水,qd.第15天两组给予兰索拉唑8 mg·kg-1,给药后不同时间点采取血样,LC-MC/MS法测定兰索拉唑及其代谢产物血药浓度,用DAS2.0软件分析其药动学参数,以考察茶多酚对兰索拉唑代谢的影响.结果:茶多酚(400 mg·kg-1·d-1)显著降低兰索拉唑(8 mg·kg-1)的AUC(0-4)、Cmax和t1/2Z(P<0.05),显著升高5-羟基兰索拉唑与兰索拉唑的AUC(0-4)比值R1(P<0.05),但对兰索拉唑砜的药动学无显著影响(P>0.05).结论:茶多酚能够显著降低兰索拉唑在大鼠体内的口服生物利用度,其原因可能与茶多酚诱导CYP2C19有关.

Effect of Tea Polyphenols on the Pharmacokinetics of Lansoprazole and its Metabolites in Rats

Objective： To evaluate the effect of tea polyphenols（TP） on the metabolism of lansoprazole in rats in vivo.Method： Sixteen rats were randomly divided into two groups： the control group and the combined group.The control group was administrated with the same volume of saline solution intragastrically while the combined group with TP 400 mg·kg-1.The administration period was 14 days.At the 15th day,both groups were given 8 mg·kg-1 lansoprazole.Plasma concentrations of lansoprazole and its metabolites were determined by LC-MS/MS.The pharmacokinetic parameters were calculated using DAS2.0 software.Result： The pharmacokinetic parameters showed that TP decreased the AUC（0-4）,Cmax and t1/2Z remarkably,increased the AUC（0-4） ratios of 5-hydroxylansoprazole to lansoprazole sulfone significantly（P0.05） while showed no significant influence on the pharmacokinetics of lansoprazole sulfone（P0.05）.Conclusion： TP can decrease the bioavailability of lansoprazole in rats significantly,which is probably related to the induction of CYP2C19 by TP.