Background and Objective

Voriconazole pharmacokinetics are highly variable in pediatric patients, and the optimal dosage has yet to be determined. The purpose of this study was to describe voriconazole pharmacokinetic and pharmacodynamic targets achieved and evaluate the efficacy and safety of voriconazole for critically ill pediatrics.

Methods

This is a single-center retrospective study conducted at a pediatric intensive care unit at a tertiary/quaternary hospital. Pediatrics admitted to the pediatric intensive care unit and who received voriconazole for a proven or suspected fungal infection with at least one measured trough concentration were included. The primary outcomes included the percentage of pediatric patients who achieved the pharmacokinetic and pharmacodynamic targets. Secondary outcomes included assessing the correlation between voriconazole trough concentrations and clinical/microbiological outcomes. All statistical analyses were performed using the R statistical software and Microsoft Excel. Multiple logistic regression was used to assess the predictors of both clinical and microbiologic cures. Multiple linear regression was used to determine significant factors associated with trough concentrations.

Results

A total of 129 voriconazole trough concentrations were measured from 71 participants at steady state after at least three doses of voriconazole. The mean (± standard deviation) of the first and second trough concentrations were 2.9 (4.2) and 2.3 (3.3) mg/L, respectively. Among the first trough concentrations, only 33.8% were within the therapeutic range (1–5 mg/L), 46.5% were below the therapeutic range, and 19.7% were above the therapeutic range. A clinical cure occurred in 78% of patients, while a microbiologic cure occurred in 80% of patients.

Conclusions

Voriconazole trough concentrations vary widely in critically ill pediatric patients and only a third of the patients achieved therapeutic concentrations with initial doses.

中文翻译：

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伏立康唑在危重儿科患者中的治疗药物监测：单中心回顾性研究

背景和目的

伏立康唑在儿童患者中的药代动力学差异很大，最佳剂量尚未确定。本研究的目的是描述所达到的伏立康唑药代动力学和药效学目标，并评估伏立康唑对危重儿科的疗效和安全性。

方法

这是一项在三级/四级医院儿科重症监护室进行的单中心回顾性研究。纳入儿科重症监护病房的儿科患者，因确诊或疑似真菌感染而接受伏立康唑治疗，并至少测量一次谷浓度。主要结局包括达到药代动力学和药效学目标的儿科患者的百分比。次要结果包括评估伏立康唑谷浓度与临床/微生物学结果之间的相关性。所有统计分析均使用 R 统计软件和 Microsoft Excel 进行。使用多元逻辑回归来评估临床和微生物治愈的预测因素。使用多元线性回归来确定与谷浓度相关的重要因素。

结果

在至少服用三剂伏立康唑后，在稳定状态下，对 71 名参与者总共测量了 129 个伏立康唑谷浓度。第一个和第二个谷浓度的平均值（±标准差）分别为 2.9 (4.2) 和 2.3 (3.3) mg/L。在第一个谷浓度中，只有33.8%在治疗范围内（1-5 mg/L），46.5%低于治疗范围，19.7%高于治疗范围。78% 的患者获得临床治愈，80% 的患者获得微生物学治愈。

结论

危重儿科患者的伏立康唑谷浓度差异很大，只有三分之一的患者在初始剂量下达到了治疗浓度。