肝移植受者术后初期万古霉素的药代动力学及药效学研究

Pharmacokinetics and pharmacodynamics of vancomycin in the liver transplanting operation recevier at the initial stage

目的 :了解肝移植术后早期并发腹膜炎患者使用万古霉素后的药代动力学、药效学及毒性情况。方法 :采用荧光偏振免疫分析仪测定用药前后不同时间血液、腹水和胆汁中万古霉素浓度 ,并以PKBP N1药代动力学程序对所测得的药物浓度 时间数据进行拟合 ,计算药代动力学参数。监测血液、腹水及胆汁中万古霉素谷浓度 ,同时观察体温、白细胞计数及肝、肾功能等药效和毒性指标。结果 :该患者静滴万古霉素后的药代动力学过程 ,在血中符合开放型三房室模型 ,其药代动力学参数t1/ 2α=5 7min ,t1/ 2 β=4 3min ,t1/ 2γ=9 2 4h ,Vss=19 881,cmax=3 1 2 9μg·ml-1,cmin=9 0 7μg·ml-1,Vc=15 981,CL =1 62 1·h-1;在腹水中符合一房室吸收模型 ,Ka=0 74 ,t1/ 2 =8 3 2h ,cmax=2 0 5 2 μg·ml-1,cmin=10 85 μg·ml-1;在胆汁中的药时数据难以用PKBP N1程序进行拟合。万古霉素谷浓度值血中为 (12 5 8± 2 5 9) μg·ml-1,腹水中为 (15 3 0± 1 5 2 ) μg·ml-1时 ,能很快缓解患者腹膜炎的临床症状 ,无肝肾毒性表现。胆汁中的万古霉素谷浓度较低 ,为 (3 11± 0 5 2 ) μg·ml-1,不能达到有效的治疗浓度。结论 :该患者使用万古霉素后的药代动力学参数与健康正常人无显著差异。在使用万古霉素时应监测血药浓度 ,

OBJECTIVE:To investigate the Pharmacokinetics,pharmacodynamics and toxicity it of vancomycin in fatients after liver transplanteration with peritonitis METHODS:Using TDX to analyse concentration of vancomycin in plasma,ascites and bile before and after using the medicine,to fit the concentration vs time data with the computer software package PKBP N1, and to calculate the parametes of pharmacodynamics Monitoring the trough concentrations of vancomycin in plasma,ascites and bile and observing the temperature, count of white blood cell, and functions of liver and kidney RESULT:Pharmacokinetic parameters of vancomycin for the patients were in plasma: t 1/2 α =5 7 min, t 1/2 β =43 min, t 1/2 γ =9 24 h, V ss =19 881, c max =31 29 μg·ml -1 , c min =9 07 μg·ml -1 , V c=15 981, CL =1 621·h -1 ;in ascite: K a=0 74, t 1/2 =8 32 h, c max =20 52 μg·ml -1 , c min =10 85 μg·ml -1 It was difficult to fit concentrations vs time data of the medicine in bile with the programme of PKBP N1 When the trough concentrations of vancomycin in plasma was (12 58±2 59)μg·ml -1 , it quickly relieved clinical symptom of peritonitis without toxicity in liver and kidney The concentration of vancomycin in bile was low and it did not achieve the effective concentration CONCLUSION: The pharmacokinetics parameter of vancomycin had no obvious difference with that of the healthy people The concentrations of plasma should be monitored when taking vancomycin to ensure applied safety and efficacy Vancomycin should not be used when gallbladder was infected