辛伐他汀对奈必洛尔在体内外代谢的影响  

The effects of simvastatin on metabolism of nebivolol in vitro and in vivo

作　　者：王鹏[1] 陈舒 程樟顺[2] Wang Peng

机构地区：[1]浙江省金华市人民医院,321000 [2]浙江省金华职业技术学院,321000

出　　处：《浙江临床医学》2022年第9期1305-1307,共3页Zhejiang Clinical Medical Journal

基　　金：金华市科学技术局公益类项目(2019-4-048);浙江省药学会医院药学专项科研资助项目(2018ZYY61)。

摘　　要：目的建立UPLC-MS/MS法测定大鼠体内外样品中奈必洛尔及其代谢产物的浓度,分析辛伐他汀在大鼠体内外对奈必洛尔代谢的影响.方法将24只雄性SD大鼠随机分成四组:A组为对照组,灌胃给予10 mg/kg奈必洛尔;B、C、D组为实验组,分别给予辛伐他汀1 mg/kg、4 mg/kg和10 mg/kg,30 min后给予10 mg/kg奈必洛尔,通过尾静脉采血并测定血药浓度.另外,建立以辛伐他汀为抑制剂,奈必洛尔为底物的大鼠肝微粒体体外孵育体系,在体外评估辛伐他汀对奈必洛尔代谢的影响.结果体内给予辛伐他汀后,与A组比较,C组Tmax显著性升高.体外不同浓度辛伐他汀对奈必洛尔表现出不同程度的抑制作用.100μmol/L浓度的辛伐他汀在大鼠肝微粒体中对奈必洛尔代谢的抑制率为18.78%,IC50值为12.67μmol/L.结论体外代谢结果显示辛伐他汀对奈必洛尔代谢有明显的抑制作用,体内研究提示辛伐他汀对大鼠体内奈必洛尔代谢无显著性影响.人体中辛伐他汀对奈必洛尔的影响有待于进一步研究.Objective To establish an UPLC-MS/MS method to determine the concentration of nebivolol and its metabolites in vivo of rats and in vitro,and to study the effect of simvastatin on nebivolol metabolism in vivo of rats and in vitro.Methods Twenty-four male Sprague-Dawley(SD)rats were randomly divided into four groups:Group A was the control group,and was given 10 mg/kg nebivolol by gavage.groups B,C,and D were the experimental groups,and 1 mg/kg,4 mg/kg or 10 mg/kg simvastatin was administered respectively.30 min later,10 mg/kg nebivolol was given.Plasma was collected from the tail vein and determined.In addition,an in vitro incubation system of rat liver microsomes with simvastatin(as an inhibitor)and nebivolol(as a substrate)was established to evaluate the its effect on the metabolism of nebivolol in rat liver microsomes.ResultsCompared with group A,the Tmax of group C were significantly increased.In vitro studies,different concentrations of simvastatin showed varying degrees of inhibitory effects on nebivolol.100μmol/L simvastatin inhibited nebivolol metabolism in rat liver microsomes by 18.78%.The IC50 value was 12.67μmol/L.ConclusionSimvastatin has no significant effect on nebivolol metabolism in rats in vivo.Since in vitro results show that simvastatin has a significant inhibitory effect on nebivolol metabolism.The effect of simvastatin on nebivolol in humans needs to be furtherstudied.

关 键 词：奈必洛尔 辛伐他汀 药物相互作用 药代动力学 

分 类 号：R965[医药卫生—药理学]