基于群体药代动力学软件优化重症感染患者万古霉素给药方案分析

Optimizing Vancomycin Dosage for Severely Infected Patients Based on Population Pharmacokinetics Software

目的分析群体药代动力学软件在优化重症感染患者万古霉素给药方案中的应用价值。方法选取上海交通大学医学院附属瑞金医院2014年2月10日至2016年12月31日使用万古霉素的重症感染成人患者137例,随机分为经验给药方案(EVR)组(65例)和优化给药方案(OVR)组(72例)。EVR组根据患者情况经验性制订给药方案,并于稳态后采用荧光偏振免疫法测定万古霉素谷浓度。OVR组采用经典药代动力学软件Vancomycin Calculator(Advanced Vancomycin Pharmacokinetics Tool)计算万古霉素初始给药剂量及初始预测谷浓度,使用群体药代动力学软件JPKD(Java PK for Desktop)校正,并预测稳态谷浓度,同时测定万古霉素实际稳态谷浓度。采用回归分析法计算OVR组谷浓度预测值与实测值的相关性;比较两组的目标谷浓度达标率及不良反应发生率。结果 OVR组稳态谷浓度预测值与实测值相关性良好(r=0.784,P <0.001);OVR组目标谷浓度达标率优于EVR组(62.50%比40.00%,P=0.010);两组肾毒性或其他不良反应发生率无显著差异。结论结合Vancomycin Calculator及JPKD软件的万古霉素优化给药法可为重症感染患者制订安全有效的个体化给药方案。

Objective To analyze the application value of population pharmacokinetic software in optimizing vancomycin dosage regimen in severely infected patients. Methods A total of 137 severely infected adult patients treated with vancomycin from February 10,2014 to December 31,2016 in Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were selected and randomly divided them into the empirical vancomycin regimen( EVR) group( 65 cases) and optimized vancomycin regimen( OVR) group( 72 cases). The EVR group made an empirical dosing plan based on the patient’s condition,and after steady-state,fluorescence polarization immunoassay was used to determine the vancomycin trough concentration. The advanced vancomycin pharmacokinetics tool,Vancomycin Calculator( VC),was used in the OVR group to calculate the initial dosage of vancomycin and the initial prediction of vancomycin trough concentration;the population pharmacokinetic software Java PK for Desktop( JPKD) was used to calibrate and predict the steady-state trough concentration,and measure the actual steady-state trough concentration of vancomycin at the same time. The regression analysis method was used to calculate the correlation between the predicted trough concentration and the actual trough concentration in the OVR group;the target trough concentration compliance rate and the incidence rate of adverse reactions of the two groups were compared. Results In the OVR group,the predicted and actual trough vancomycin concentrations were significantly correlated( r = 0. 784,P < 0. 001). The target trough concentration attainment rate in the OVR group was better than that in the EVR group( 62. 50% vs. 40. 00%,P = 0. 010);there was no significant difference in the incidence of nephrotoxicity or other adverse reactions between the two groups. Conclusion The optimized vancomycin administration method combined with VC and JPKD software can formulate a safe and effective individualized dosage regimen for severely infected patients.