Department of pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
J Clin Pharm Ther. 2020 Dec;45(6):1278-1287. doi: 10.1111/jcpt.13206. Epub 2020 Jun 18.
Augmented renal clearance (ARC) is characterized by enhanced renal clearance, which leads to insufficient vancomycin exposure and treatment failure. In haematologic malignancy patients, determination of optimal vancomycin dosage is essential because of high stake of life-threatening bacterial infection and increased clearance. The aim of this study was to describe vancomycin pharmacokinetic parameters in haematologic malignancy with augmented renal clearance children and define the appropriate dosing regimen to achieve an AUC /MIC ≥400.
Hematologic malignancy with ARC children was enrolled in this retrospective study. The vancomycin PPK model was established by non-linear mixed-effects modelling programme. Goodness-of-fit (GOF) plots, non-parametric bootstrap, normalized prediction distribution error (NPDE) and visual predictive checks (VPCs) were carried out for internal evaluation of the final model. Monte Carlo simulation method was used to stimulate the optimal dosage regimens.
Fifty-three patients with 106 samples were included. A one-compartment model with first-order elimination was developed, and the final model was as follows: CL (L/h) = 6.32×（WT/70） × e ; V(L) = 39.6×(WT/70), where WT denotes weight (kg). The internal validation of the model showed a good prediction performance. Monte Carlo simulation results showed that when MIC was 0.5 mg/L or 1 mg/L, the recommended doses to achieve a target of AUC /MIC ≥400 were 25 to 40 and 50 to 75 mg/kg/d, respectively. With decreasing weight, the recommended dosage to achieve an AUC /MIC ≥400 increased.
A one-compartment vancomycin PPK model was established in haematologic malignancy with augmented renal clearance children with weight with allometric scaling as a significant covariate. When MIC was 1 mg/L, current recommended paediatric dosages were insufficient in haematologic malignancy with augmented renal clearance children and should be increased.
增强的肾清除率（ARC）的特征在于增强的肾清除率，这导致万古霉素暴露不足和治疗失败。在血液恶性肿瘤患者中，由于危及生命的细菌感染风险增加和清除率增加，确定最佳万古霉素剂量至关重要。本研究的目的是描述血液恶性肿瘤 ARC 儿童的万古霉素药代动力学参数，并确定适当的给药方案，以实现 AUC/MIC≥400。
本回顾性研究纳入了 ARC 血液恶性肿瘤儿童。采用非线性混合效应模型程序建立万古霉素 PPK 模型。采用拟合优度（GOF）图、非参数自举法、归一化预测分布误差（NPDE）和可视化预测检查（VPCs）对内评估最终模型。采用蒙特卡罗模拟方法模拟最佳剂量方案。
纳入 53 例患者（106 个样本）。建立了一个一室模型，具有一级消除，最终模型如下：CL（L/h）=6.32×（WT/70）×e；V（L）=39.6×（WT/70），其中 WT 表示体重（kg）。模型的内部验证表明其具有良好的预测性能。蒙特卡罗模拟结果表明，当 MIC 为 0.5mg/L 或 1mg/L 时，分别达到 AUC/MIC≥400 的目标推荐剂量为 25-40mg/kg/d 和 50-75mg/kg/d。随着体重的减轻，达到 AUC/MIC≥400 的推荐剂量增加。
建立了一个以体重为重要协变量的血液恶性肿瘤 ARC 儿童的单室万古霉素 PPK 模型。当 MIC 为 1mg/L 时，目前推荐的儿科剂量在血液恶性肿瘤 ARC 儿童中不足，应增加。
