七叶皂苷对洛伐他汀在高脂血症大鼠模型体内药代动力学的影响  

Effects of escin on the pharmacokinetics of lovastatin in hyperlipidemic rats

作　　者：吴秀君[1] 苑冬敏[1] 陈克研 马然[1] 韩波[1] 于艳[1] WU Xiu-jun;YUAN Dong-min;CHEN Ke-yan;MA Ran;HAN Bo;YU Yan(Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China;College of Basic Medical Science,China Medical University,Shenyang 110122,China)

机构地区：[1]辽宁中医药大学附属医院,辽宁沈阳110032 [2]中国医科大学基础医学院,辽宁沈阳110122

出　　处：《实用药物与临床》2020年第3期212-216,共5页Practical Pharmacy and Clinical Remedies

基　　金：辽宁省自然基金课题(201602498)。

摘　　要：目的在高脂血症大鼠模型中研究七叶皂苷对洛伐他汀药代动力学的影响。方法采用高脂饲料喂饲大鼠,构建高脂血症大鼠模型,通过血清生化分析确定造模成功。选择12只造模成功的大鼠,随机分成2组,即单独给药组和联合给药组,每组6只大鼠。单独给药组和联合给药组大鼠分别经尾静脉注射给予0.9%生理盐水和注射用七叶皂苷钠(0.5 mg/kg,qd),连续14 d。第14天,给药后,两组大鼠灌胃给予洛伐他汀(20 mg/kg,0.5%CMC-Na溶液),并于洛伐他汀给药前和给药后不同时间点采集血样,采用HPLC-MS/MS方法测定洛伐他汀及其活性代谢物洛伐他汀酸的血药浓度,计算药动学参数。结果长期给予七叶皂苷钠导致洛伐他汀酸的血浆暴露水平显著升高,Cmax、AUC0-t、AUC0-∞分别是单独给药组的2.43(90%CI:1.55,3.31)、2.66(90%CI:1.67,3.66)和2.99倍(90%CI:1.44,4.55),两组比较差异有统计学意义(P<0.05)。与单独给药组相比,联合给药组洛伐他汀的血浆暴露也略有增加,但两组Cmax和AUC比较差异无统计学意义(P>0.05)。结论七叶皂苷可抑制高脂血症模型大鼠的洛伐他汀代谢,增加其体内暴露水平。Objective To establish the hyperlipidemia rat model,and study the effect of escin on the pharmacokinetics of lovastatin in hyperlipidemia rat model.Methods The hyperlipidemia rat model was induced by high-fat diet and confirmed by serum biochemical analysis.Twelve hyperlipidemia rats were randomly divided into two groups:lovastatin group and lovastatin combined with escin group(combined group).The rats in both groups were given lovastatin(20 mg/kg,0.5%CMC-Na solution)after receiving escin(for combined group)or saline(for lovastatin group)for 14 days.Blood samples were collected at different time points before and after administration of lovastatin.The plasma concentration of lovastatin and lovastatin acid(an active metabolite’s of lovastatin)were determined by LC-MS/MS method,and pharmacokinetics parameters were calculated.Results Long-term administration of lovastatin resulted in a significant increase in the plasma exposure of lovastatin acid in the hyperlipidemic rat model,and the corresponding mean Cmax,AUC0-t and AUC0-∞in combined group were 2.43(90%CI:1.55,3.31),2.66(90%CI:1.67,3.66)and 2.99(90%CI:1.44,4.55)-fold in those of lovastatin group,respectively.There were significant differences between the two groups(P<0.05).The plasma exposure of lovastatin was also increased,however,the difference in terms of Cmax and AUC between the two groups was not significant(P>0.05).Conclusion Escin can inhibit the metabolism of lovastatin in hyperlipidemic rats and increase its exposure in vivo.

关 键 词：洛伐他汀 洛伐他汀酸 七叶皂苷 药代动力学 高脂血症 

分 类 号：R285.5[医药卫生—中药学]