首页|丹参主要活性成分对瑞格列奈体外代谢性相互作用影响

丹参主要活性成分对瑞格列奈体外代谢性相互作用影响

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  • 国家科技期刊平台
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目的 基于细胞色素P450(CYP450)酶代谢机制考察丹参主要有效成分丹参酮Ⅰ、隐丹参酮和丹参酮Ⅱ A磺酸钠对瑞格列奈代谢的影响，从而为临床安全合理用药提供参考。方法 建立大鼠和人肝微粒体体外孵育体系，分别以0。25～50 μmol/L的丹参酮Ⅰ、隐丹参酮和丹参酮Ⅱ A磺酸钠与瑞格列奈(大鼠肝微粒体中浓度44 μmol/L和人肝微粒体5。5μmol/L)于37 ℃水浴中共同孵育，并以阿托伐他汀为内标，应用UPLC法测定肝微粒体中瑞格列奈的剩余浓度，最后通过肝微粒体中瑞格列奈的减少量，考察3种成分对瑞格列奈代谢的影响。结果 丹参酮Ⅰ在浓度为50 μmol/L时，在大鼠和人肝微粒体中瑞格列奈剩余量的百分比分别为98。11％、96。50％;隐丹参酮浓度为50 μmol/L时，在大鼠和人肝微粒体中瑞格列奈剩余量的百分比分别为102。37％、84。69％;丹参酮Ⅱ A磺酸钠注射液10、50 μmol/L在大鼠和人肝微粒体中表现出抑制作用，其在大鼠和人肝微粒体孵育体系中对瑞格列奈半数抑制浓度分别为0。17、0。33 μmol/L。结论 丹参酮Ⅰ和隐丹参酮在大鼠肝微粒体中对瑞格列奈的代谢无明显的影响，而在人肝微粒体实验中隐丹参酮表现出对瑞格列奈代谢的轻度诱导作用;丹参酮Ⅱ A磺酸钠对瑞格列奈不论在大鼠还是人肝微粒体中均表现出较强的抑制作用。故丹参酮Ⅱ A磺酸钠注射液与瑞格列奈合用时应注意监测血糖，以免患者发生低血糖事件。
Effects of Main Active Components of Salvia Miltiorrhiza on Metabolic Interaction of Repaglinide in vitro
Objective Based on the metabolic mechanism of cytochrome P450(CYP450)enzyme,the effects of the main active ingredients of Salvia Miltiorrhiza,tanshinone Ⅰ,cryptotanshinone,and sodium tanshinone ⅡA sulfonate on the metabolism of repaglinide were studied,so as to provide reference for clinically safe and rational drug use.Methods The in vitro incubation systems were established for rat and human liver microsomes,co-incubated in a 37℃ water bath with concentrations ranging 0.25-50 μ mol/L tanshinone Ⅰ,cryptotanshinone,and tanshinone Ⅱ A sodium sulfonate and repaglinide(concentration in rat liver microsomes 44 μ mol/L and human liver microsomes 5.5 μ mol/L),respectively.The residual concentration of repaglinide in liver microsomes was determined by UPLC with atorvastatin as the internal standard.Finally,the effects of three components on the metabolism of repaglinide were observed by reduced amount of repaglinide in liver microsomes.Results When the concentration of tanshinone Ⅰ was 50 μ mol/L,the percentage of residual repaglinide in rat and human liver microsomes was 98.11％and 96.50％respectively.When the concentration of cryptotanshinone was 50 μ mol/L,the percentage of residual repaglinide in rat and human liver microsomes was 102.37％and 84.69％respectively.Tanshinone Ⅱ A Sodium Sulfonate Injection 10 and 50 μ mol/L showed inhibitory effects on rat and human liver microsomes,and its half inhibitory concentration on repaglinide in rat and human liver microsomes incubation system was 0.17 and 0.33 μ mol/L respectively.Conclusions Tanshinone Ⅰ and cryptotanshinone had no obvious effect on the metabolism of repaglinide in rat liver microsomes,while cryptotanshinone had a slight induction effect on the metabolism of repaglinide in human liver microsomes.Tanshinone Ⅱ A sulfonate sodium had a strong inhibitory effect on repaglinide in both rat and human liver microsomes.Therefore,when Tanshinone Ⅱ A Sodium Sulfonate Injection was used in combination with repaglinide,blood glucose should be monitored to avoid hypoglycemic events in patients.

tanshinone Ⅰcryptotanshinonesodium tanshinone Ⅱ A sulfonateRepaglinidecytochrome P450drug-drug interactionultra-high performance liquid phaseChinese herbal medicine

何文娟、刘秀菊、孙倩、赵晓娟、李敬瑄、王淑梅

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河北医科大学第二医院药学部(石家庄 050000)

丹参酮Ⅰ 隐丹参酮 丹参酮ⅡA磺酸钠 瑞格列奈 细胞色素P450酶 药物相互作用 超高效液相 中药

河北省中医药类科研指令性计划(2021)

2121132

2024

10.7661/j.cjim.20230508.131

中国中西医结合杂志
中国中西医结合学会 中国中医科学院

中国中西医结合杂志

CSTPCD北大核心
影响因子：2.149
ISSN：1003-5370
年,卷(期)：2024.44(1)
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