伊伐布雷定肝脏转运机制的初步研究

目的：探讨伊伐布雷定肝脏转运与OCT1的相关性。方法：将雄性SD大鼠分为对照组与实验组，对照组伊伐布雷定（1 mg·kg^-1）灌胃给药，实验组OCT1抑制剂雷尼替丁（0.8 mg·kg^-1）和伊伐布雷定（1.0 mg·kg^-1）相继灌胃给药，比较2组间伊伐布雷定的药动学参数；采用原代肝细胞，分为对照组：伊伐布雷定（0.2，0.5，1 μmol·L^-1）；实验组：雷尼替丁（0.5，1.0，2.0 μmol·L^-1）+伊伐布雷定（0.2，0.5，1 μmol·L^-1），探讨雷尼替丁对伊伐布雷定肝脏摄取的影响。结果：合用雷尼替丁后，伊伐布雷定药动学参数C_max、AUC_0-t、AUC_0-∞分别增加了115.41%，128.73%，128.05%，而CLz/F值降低了56.35%，差异有显著性（P<0.05或P<0.01）。雷尼替丁明显抑制肝细胞对伊伐布雷定的摄取，抑制作用随雷尼替丁的浓度增加而增强。结论：伊伐布雷定肝脏转运很可能与OCT1有关。

Preliminary investigation on the uptake mechanism of ivabradine in liver

OBJECTIVE To preliminarily verify that the uptake of ivabradine in liver was related to OCT1.METHODS The experiment was divided into ivabradine control group (0.2, 0.5, 1 μmol·L^-1) and ivabradine (0.2, 0.5, 1 μmol·L^-1)+ranitidine (0.5, 1.0, 2.0 μmol·L^-1) experimental group. Male SD rats (225±20) g were randomly divided into control group and experimental group. Rats in the former group were administered ivabradine (1 mg·kg^-1) by oral route, and rats in the latter group were co-administered ivabradine (1 mg·kg^-1) and ranitidine (0.8 mg·kg^-1) by oral route. The pharmacokinetic parameters of two groups were compared to explore the effect of ranitidine on uptake of ivabradine in the primary live cells.RESULTS The C_max, AUC_0-t and AUC_0-∞ of ivabradine in rats increased by 115.41%, 128.73% and 128.05%, respectively. The CLz/F decreased by 56.35%. The uptake of ivabradine in liver cells was inhibited by ranitidine in a concentration-dependent manner.CONCLUSION The uptake of ivabradine in liver is likely to be related to the OCT1.