杨欣怡;戴国梁;陈闪闪;李瑶;刘美琛;李斐然;曹阳;王一清;居文政;
YANG Xin-yi;DAI Guo-liang;CHEN Shan-shan;LI Yao;LIU Mei-chen;LI Fei-ran;CAO Yang;WANG Yi-qing;JU Wen-zheng;Affiliated Hospital of Nanjing University of Chinese Medicine;

• 1:南京中医药大学附属医院

摘要(Abstract)：

建立了同时测定慢性不可预知性温和应激(CUMS)抑郁模型大鼠血浆交泰丸(含木兰花碱、药根碱、小檗红碱、黄连碱、小檗碱)及氟西汀共6种成分浓度的LC-MS/MS分析。6种成分线性关系良好，专属性、准确度、精密度、稳定性等方法学均符合生物样品分析要求。采用DAS 3.2.2软件计算药代动力学参数，结果表明6种成分体内代谢过程表现均符合非房室模型特征。交泰丸与氟西汀联用后，交泰丸中木兰花碱的AUC_(0-t)、AUC_(0-∞)、C_(max)、C_(av)均显著升高(P<0.05),小檗红碱的药动学变化趋势与木兰花碱相反，其AUC_(0-t)、AUC_(0-∞)、T_(max)、C_(max)、C_(av)均显著下降(P<0.01,P<0.05);药根碱、黄连碱、小檗碱与小檗红碱的药动学变化趋势一致；氟西汀单用或联用的药动学特征无显著变化。结果提示交泰丸与氟西汀联用后抗抑郁药效增强可能与氟西汀影响交泰丸中有效成分的药动学特征有关。
A high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) was developed for simultaneously determining the components(magnoflorine, jatrorrhizine, berberrubine, coptisine, berberine) of Jiaotai Pills and Fluoxetine in plasma of rats with chronic unpredictable mild stress(CUMS)-induced depression to investigate the pharmacokinetic herb-drug interaction of Jiaotai Pills and Fluoxetine in the rats. The six components showed good linear relationship within the corresponding concentration ranges, and the method showed high specificity, accuracy, precision, and stability. Their pharmacokinetic parameters were calculated by DAS 3.2.2, and the results showed that the in vivo metabolic processes of the six components accorded with the characteristics of non-compartmental model. When Jiaotai Pills and Fluoxetine were used together, the AUC_(0-t), AUC_(0-∞), C_(max), and C_(av) of magnoflorine all significantly increased(P<0.05), while the pharmacokinetic trend of berberrubine was opposite to that of magnoflorine, as manifested by the decrease in AUC_(0-t), AUC_(0-∞), T_(max), C_(max), and C_(av)(P<0.01, P<0.05). The pharmacokinetic characteristics of jatrorrhizine, coptisine, and berberine followed the trend of berberrubine. There was no significant difference in the pharmacokinetic characteristics of Fluoxetine in the single or combination groups. This study suggests that the enhanced antidepressant efficacy of Jiaotai Pills and Fluo-xetine may be attributed to the pharmacokinetic interaction.

关键词(KeyWords)： 交泰丸;氟西汀;抑郁;药动学
Jiaotai Pills;Fluoxetine;depression;pharmacokinetic

Abstract:

Keywords:

基金项目(Foundation): 江苏省基础研究计划项目(BK20211394);; 江苏省中医药领军人才项目(SLJ0208)

作者(Authors): 杨欣怡;戴国梁;陈闪闪;李瑶;刘美琛;李斐然;曹阳;王一清;居文政;
YANG Xin-yi;DAI Guo-liang;CHEN Shan-shan;LI Yao;LIU Mei-chen;LI Fei-ran;CAO Yang;WANG Yi-qing;JU Wen-zheng;Affiliated Hospital of Nanjing University of Chinese Medicine;

DOI: 10.19540/j.cnki.cjcmm.20220606.501

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