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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DAS 2.0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。
Objective: To study the effects of tea polyphenols on the pharmacokinetics of lansoprazole and its metabolites 5-hydroxy-lansoprazole and lansoprazole sulfone in rats. Methods: Twenty-six male Sprague-Dawley rats were randomly divided into two groups: drug-alone group and combination group. The first 14 d groups were given gavage 400 mg · kg-1 of tea polyphenols, . On the fifteenth day, the two groups were given lansoprazole 8 mg.kg-1, blood samples were taken at different time points after administration, and plasma concentrations of lansoprazole and its metabolites were determined by LC-MC / MS. The pharmacokinetic parameters to investigate the effect of tea polyphenols on the metabolism of lansoprazole. Results: AUC (0-4), Cmax and t1 / 2Z (P <0.05) of lansoprazole (8 mg.kg-1) were significantly decreased by 400 mg.kg-1.d- (P <0.05), but did not affect the pharmacokinetics of lansoprazole sulfone significantly (P> 0.05). Conclusion: Tea polyphenols can significantly reduce the oral bioavailability of lansoprazole in rats, the reason may be related to tea polyphenols induced CYP2C19.