PDF(Pubmed)
Abstract：
Introduction: While vancomycin remains a widely prescribed antibiotic, it can cause ototoxicity and nephrotoxicity, both of which are concentration-associated. Overtreatment can occur when the treatment lasts for an unnecessarily long time. Using a model-informed precision dosing scheme, this study aims to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model for vancomycin to determine the optimal dosage regimen and treatment duration in order to avoid drug-induced toxicity. Methods: The data were obtained from electronic medical records of 542 patients, including 40 children, and were analyzed using NONMEM software. For PK, vancomycin concentrations were described with a two-compartment model incorporating allometry scaling. Results and discussion: This revealed that systemic clearance decreased with creatinine and blood urea nitrogen levels, history of diabetes and renal diseases, and further decreased in women. On the other hand, the central volume of distribution increased with age. For PD, C-reactive protein (CRP) plasma concentrations were described by transit compartments and were found to decrease with the presence of pneumonia. Simulations demonstrated that, given the model informed optimal doses, peak and trough concentrations as well as the area under the concentration-time curve remained within the therapeutic range, even at doses smaller than routine doses, for most patients. Additionally, CRP levels decreased more rapidly with the higher dose starting from 10 days after treatment initiation. The developed R Shiny application efficiently visualized the time courses of vancomycin and CRP concentrations, indicating its applicability in designing optimal treatment schemes simply based on visual inspection.
摘要：
简介：虽然万古霉素仍然是一种广泛使用的抗生素，会引起耳毒性和肾毒性,两者都与浓度相关。当治疗持续不必要的长时间时，可能会发生过度治疗。使用模型通知的精确给药方案，本研究旨在建立万古霉素的群体药代动力学(PK)和药效学(PD)模型,以确定最佳给药方案和治疗持续时间,从而避免药物引起的毒性.方法：数据来自542例患者的电子病历，包括40个孩子,并使用NONMEM软件进行分析。对于PK，万古霉素浓度用两室模型描述，该模型包含异速比。结果和讨论：这表明全身清除率随着肌酐和血尿素氮水平而降低，糖尿病和肾脏疾病的历史，女性人数进一步减少。另一方面,中心分布量随年龄增长而增加。对于PD，C反应蛋白（CRP）血浆浓度由转运室描述，并发现随着肺炎的存在而降低。模拟表明，给定模型的最佳剂量，峰和谷浓度以及浓度-时间曲线下的面积保持在治疗范围内，即使剂量小于常规剂量，对于大多数患者来说。此外,从治疗开始后10天开始，较高剂量的CRP水平下降更快。开发的RShiny应用程序有效地可视化万古霉素和CRP浓度的时间进程，表明其在简单地基于视觉检查设计最佳治疗方案中的适用性。
