Garner Lauren M, Ngo Susan, Kaplan Jenna Bognaski, Wilson William S, McKinzie Cameron J
J Pediatr Pharmacol Ther. 2021;26(8):834-840. doi: 10.5863/1551-6776-26.8.834. Epub 2021 Nov 10.
Initial posaconazole dosing regimens in children often do not achieve target concentrations, and data continue to support the need for higher initial dosing regimens. The objective of this study is to contribute to the current data regarding suboptimal posaconazole dosing in pediatric patients by retrospectively observing dosing strategies and subsequent drug concentrations.
This study was conducted at a single institution in 27 patients aged 1 to 21 years. Patients who were initiated on any formulation of posaconazole for prophylaxis or treatment while admitted to the hospital were included. The primary outcome was to determine the percentage of pediatric patients who achieved the targeted trough concentration using their initial posaconazole dosing regimen. Secondary outcomes included percentage of patients who experienced a breakthrough invasive fungal infection (IFI), percentage of patients with elevated liver function tests (LFTs), and discontinuation for any reason.
There were 15 patients (55.5%) who reached desired trough serum concentration after the initial dosing regimen. The number of dose modifications to achieve the desired trough ranged from 1 to 3. Most patients received delayed-release tablets (n = 17), and the average doses for reaching prophylactic and treatment trough concentrations were 6.1 mg/kg/day and 11 mg/kg/day, respectively. There were 2 patients (7.4%) who experienced breakthrough IFI. Overall, 5 patients developed elevated LFTs and 7 patients discontinued treatment early.
The results describe a single population of pediatric patients, of whom 55% were able to achieve target trough concentrations of posaconazole with the initial dosing strategy used.
儿童初始泊沙康唑给药方案往往无法达到目标浓度，现有数据持续支持需要更高的初始给药方案。本研究的目的是通过回顾性观察给药策略及随后的药物浓度，为目前关于儿科患者泊沙康唑给药不足的数据提供补充。
本研究在一家机构对27例年龄1至21岁的患者开展。纳入住院期间开始使用任何剂型泊沙康唑进行预防或治疗的患者。主要结局是确定使用初始泊沙康唑给药方案达到目标谷浓度的儿科患者百分比。次要结局包括发生突破性侵袭性真菌感染（IFI）的患者百分比、肝功能检查（LFT）升高的患者百分比以及因任何原因停药的情况。
15例患者（55.5%）在初始给药方案后达到了期望的谷血清浓度。为达到期望谷浓度而进行的剂量调整次数为1至3次。大多数患者接受缓释片（n = 17），达到预防和治疗谷浓度的平均剂量分别为6.1 mg/kg/天和11 mg/kg/天。有2例患者（7.4%）发生突破性IFI。总体而言，5例患者LFT升高，7例患者提前停药。
研究结果描述了一组儿科患者，其中55%使用所采用的初始给药策略能够达到泊沙康唑的目标谷浓度。
