以药代动力学检测指标探讨血必净注射液联合左氧氟沙星治疗急性胰腺炎的增效作用机制  

Study on the synergistic mechanism of Xuebijing injection combined with levofloxacin in the treatment of acute pancreatitis from the perspective of pharmacokinetics

作　　者：杨巧虹[1] 姚高琼[2] 周远大[2] 贾春燕 杨辉[2] YANG Qiaohong;YAO Gaoqiong;ZHOU Yuanda;JIA Chunyan;Yanghui(Chongqing Quality Testing&Inspection Centre for Medical Devices,Chongqing 401147,China;Department of Pharmacy,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China;School of Pharmacy,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医疗器械质量检验中心,重庆401147 [2]重庆医科大学附属第一医院药学部,重庆400016 [3]重庆医科大学药学院,重庆400016

出　　处：《国际检验医学杂志》2021年第17期2084-2089,共6页International Journal of Laboratory Medicine

基　　金：重庆市科卫联合医学科研项目(2018MSXM055)。

摘　　要：目的研究血必净注射液对左氧氟沙星在胰腺组织中分布的影响,以探讨血必净注射液联合左氧氟沙星治疗急性胰腺炎的新机制。方法将108只小鼠随机分为实验组和对照组,每组54只。实验组和对照组在实验前3 d分别腹腔注射血必净22 mL/kg或等体积0.9%氯化钠注射液,于末次给药1 h后各组动物均静脉注射左氧氟沙星132 mg/kg,分别于给药后3、5、10、30、60、120、240、480、720 min对每组6只小鼠采集血液标本和胰腺组织,制为血浆或胰腺组织匀浆,冷藏待测。采用高效液相色谱(HPLC)法检测标本中左氧氟沙星质量浓度,DAS2.0软件计算药代动力学参数。结果对照组和实验组小鼠静脉注射左氧氟沙星后血浆和胰腺组织中药物质量浓度-时间曲线(简称为药-时曲线)均符合二室模型。对照组和实验组小鼠血浆中左氧氟沙星0~12 h药-时曲线下面积(AUC0-12)分别为(223.57±23.42)和(192.02±20.34)μg·h/mL,两组间比较差异有统计学意义(P<0.05);表观分布容积(Vd)分别为(0.08±0.01)和(0.07±0.01)L/kg,两组间比较差异有统计学意义(P<0.05)。对照组和实验组小鼠胰腺组织中,左氧氟沙星AUC0-12分别为(171.42±30.00)和(223.68±25.96)μg·h/mL(P<0.05),Vd分别为(0.08±0.02)和(0.13±0.04)L/kg,两组间比较差异均有统计学意义(P<0.05)。结论血必净注射液可以明显提高左氧氟沙星在胰腺组织中的药物质量浓度。Objective To study the effect of Xuebijing injection on the distribution of levofloxacin(LVFX)in pancreatic tissue,and to explore the new mechanism of Xuebijing injection combined with LVFX in the treatment of acute pancreatitis.Methods A total of 108 mice were randomly divided into the experimental group and the control group,with 54 rats in each group.The experimental group and the control group were intraperitoneally injected with Xuebijing injection 22 mL/kg or equal volume 0.9%sodium chloride injection 3 days before the experiment.One hour after the last dose,all the animals were intravenously injected with 132 mg/kg LVFX,and the blood samples and pancreas tissue were collected for the 6 mice in each group at different time points 3,5,10,30,60,120,240,480 and 720 min,respectively.The plasma or pancreatic tissue homogenate samples were kept in cold storage.Concentrations of LVFX in the plasma and pancreatic tissues were detected by high performance liquid chromatography(HPLC),and pharmacokinetic parameters were calculated with DAS2.0 software.Results After intravenous injection of levofloxacin in the control group and the experimental group,the drug-time curves of the blood and pancreas tissues both fit the two-compartment model.The AUC0-12 values of levofloxacin in the blood of mice in the control group and the experimental group were(223.57±23.42)and(192.02±20.34)μg·h/mL,respectively,and there was statistically significant difference between the two groups(P<0.05);the Vd values were(0.08±0.01)and(0.07±0.01)L/kg,respectively,and there was statistically significant difference between the two groups(P<0.05).In the pancreatic tissue of the control group and the experimental group,the AUC0-12 values of levofloxacin were(171.42±30.00)and(223.68±25.96)μg·h/mL(P<0.05),and the Vd values were(0.08±0.02)and(0.13±0.04)L/kg,respectively,and the differences between the two groups were both statistically significant(P<0.05).Conclusion Xuebijing injection can significantly increase the concentration of LVFX in

关 键 词：血必净注射液 左氧氟沙星 胰腺组织 高效液相色谱法 组织分布 

分 类 号：R965[医药卫生—药理学]