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Application of Pharmacometrics in Pharmacotherapy: Open-Source Software for Vancomycin Therapeutic Drug Management

机译:药效测学在药物治疗中的应用:万古霉素治疗药物管理的开源软件

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摘要

The population pharmacokinetic (PK) parameters that are implemented in therapeutic drug management (TDM) software were generally obtained from a Western population and might not be adequate for PK prediction with a Korean population. This study aimed to develop a population PK model for vancomycin using Korean data to improve the quality of TDM for Korean patients. A total of 220 patients (1020 observations) who received vancomycin TDM services were included in the dataset. A population PK analysis was performed using non-linear mixed effects modeling, and a covariate evaluation was conducted. A two-compartment model with first-order elimination best explained the vancomycin PK, with estimates of 2.82 L/h, 31.8 L, 11.7 L/h, and 75.4 L for CL, V1, Q, and V2, respectively. In the covariate analysis, weight correlated with the volume of the peripheral compartment, and creatinine clearance, hemodialysis, and continuous renal replacement therapy treatments contributed to the clearance of vancomycin. The results show the clear need to optimize the PK parameters used for TDM in Korean patients. Specifically, V1 should be smaller for Korean patients, and renal replacement therapies should be considered in TDM practice. This final model was successfully applied in R shiny as open-source software for Koreans.
机译:在治疗药物管理(TDM)软件中实施的人口药代动力学(PK)参数通常从西方人民群中获得,并且可能不适合与韩国人群的PK预测。本研究旨在使用韩国数据开发用于万古霉素的人口PK模型,提高韩国患者的TDM质量。在数据集中包含共有220名接受万古霉素TDM服务的患者(1020名观察)。使用非线性混合效果建模进行群体PK分析,并进行协变量评价。具有一阶消除的双隔室模型最能解释万古霉素PK,估计分别为Cl,V1,Q和V2的2.82L / h,31.8L,11.7L / h和75.4L。在调节分析中,重量与周边隔室的体积相关,肌酐清除,血液透析和连续肾脏替代治疗治疗有助于Vancomcin的间隙。结果表明,清楚需要优化韩国患者中用于TDM的PK参数。具体而言,V1对于韩国患者应该小,而TDM实践应考虑肾置换疗法。该最终模型成功应用于R闪亮,作为韩国人的开源软件。

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