Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, MBC 11, P.O. Box 3354, 11211, Riyadh, Saudi Arabia.
Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Paediatr Drugs. 2024 Mar;26(2):197-203. doi: 10.1007/s40272-023-00616-4. Epub 2024 Jan 16.
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.
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.
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.
Voriconazole trough concentrations vary widely in critically ill pediatric patients and only a third of the patients achieved therapeutic concentrations with initial doses.
伏立康唑在儿科患者中的药代动力学具有高度变异性，尚未确定最佳剂量。本研究旨在描述伏立康唑药代动力学和药效学目标的实现，并评估伏立康唑治疗危重症儿科患者的疗效和安全性。
这是一项在三级/四级医院儿科重症监护病房进行的单中心回顾性研究。纳入在儿科重症监护病房住院且至少有一次测量的谷浓度的患儿，这些患儿接受伏立康唑治疗确诊或疑似真菌感染。主要结局包括达到药代动力学和药效学目标的儿科患者比例。次要结局包括评估伏立康唑谷浓度与临床/微生物学结局的相关性。所有统计分析均使用 R 统计软件和 Microsoft Excel 进行。多因素逻辑回归用于评估临床和微生物学治愈率的预测因素。多元线性回归用于确定与谷浓度相关的显著因素。
在至少接受三次伏立康唑治疗后，稳态时从 71 名患者中测量了 129 个伏立康唑谷浓度。第一次和第二次谷浓度的平均值（±标准差）分别为 2.9（4.2）和 2.3（3.3）mg/L。在第一次谷浓度中，只有 33.8%在治疗范围内（1-5mg/L），46.5%低于治疗范围，19.7%高于治疗范围。78%的患者临床治愈，80%的患者微生物学治愈。
危重症儿科患者的伏立康唑谷浓度差异很大，初始剂量仅三分之一的患者达到治疗浓度。
