Du Xiaohuan, Yan Yinghui, Li Fang, Zhou Mi, Yang Mengjie, Hu Shaoyan, Ling Jing, Yuan Shuwei, Wang Wenjing, Gu Chao, Zhu Zengyan, Wang Wenjuan
Department of Pharmacy, Children's Hospital of Soochow University, Suzhou, China.
Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
Transl Pediatr. 2025 Jan 24;14(1):4-13. doi: 10.21037/tp-24-400. Epub 2025 Jan 21.
Posaconazole oral suspension is not approved for use in children younger than 13 years of age, and the optimal dosing regimen is unclear. The target trough concentration of posaconazole for the effective prevention of invasive fungal infections in adults is influenced by multiple factors, but reports in children aged <13 years remain limited. Therefore, the primary objective of this study was to evaluate potential risk factors affecting the steady-state trough concentration of oral posaconazole suspension in a large population of Chinese children.
This observational, single-center study retrospectively analyzed pediatric patients younger than 13 years of age who received posaconazole oral suspension for the prevention of invasive fungal disease and implemented therapeutic drug monitoring (TDM) from January 2020 to July 2022.
A total of 132 children with 922 steady-state trough concentrations of posaconazole were included in this study. The median dosage of posaconazole by standardized body weight was 14.2 (range, 4.2-51.2) mg/kg/day, with considerable variability. The median posaconazole concentration was 0.81 (range, 0.05-4.5) µg/mL, and the proportion of children reaching the recommended target concentration (≥ 0.7 µg/mL) was 59.5%. The highest percentage of the target concentration (76.8%) was achieved at a median daily dosage of 18 (range, 17-19) mg/kg/day of posaconazole. Multivariate linear regression analysis revealed significant positive correlations between albumin levels (P=0.004) and weight (P<0.001) and posaconazole concentrations. Conversely, treatment with hematopoietic stem cell transplantation (P=0.004), the occurrence of diarrhea (P=0.003), and the coadministration of omeprazole (P<0.001), famotidine (P=0.001) and methylprednisolone (dosage ≥0.7 mg/kg/day) (P=0.006) were associated with significantly reduced posaconazole concentrations.
In children under 13 years of age, administration of a dosage regimen of 18 (range, 17-19) mg/kg/day of posaconazole suspension resulted in a higher proportion of children achieving the recommended target concentration. Multiple factors had significant effects on posaconazole trough concentrations. TDM is important for identifying suboptimal posaconazole exposure and making timely dose adjustments.
泊沙康唑口服混悬液未被批准用于13岁以下儿童，且最佳给药方案尚不清楚。泊沙康唑在成人中有效预防侵袭性真菌感染的目标谷浓度受多种因素影响，但13岁以下儿童的相关报道仍然有限。因此，本研究的主要目的是评估影响大量中国儿童口服泊沙康唑混悬液稳态谷浓度的潜在风险因素。
这项观察性单中心研究回顾性分析了2020年1月至2022年7月期间接受泊沙康唑口服混悬液预防侵袭性真菌病并进行治疗药物监测（TDM）的13岁以下儿科患者。
本研究共纳入132名儿童，其泊沙康唑稳态谷浓度达922次。按标准体重计算，泊沙康唑的中位剂量为14.2（范围4.2 - 51.2）mg/kg/天，存在较大变异性。泊沙康唑中位浓度为0.81（范围0.05 - 4.5）μg/mL，达到推荐目标浓度（≥0.7μg/mL）的儿童比例为59.5%。泊沙康唑中位日剂量为18（范围17 - 19）mg/kg/天时，目标浓度的百分比最高（76.8%）。多变量线性回归分析显示白蛋白水平（P = 0.004）、体重（P < 0.001）与泊沙康唑浓度之间存在显著正相关。相反，造血干细胞移植治疗（P = 0.004）、腹泻的发生（P = 0.003）以及奥美拉唑（P < 0.001）、法莫替丁（P = 0.001）和甲泼尼龙（剂量≥0.7mg/kg/天）（P = 0.006）的联合使用与泊沙康唑浓度显著降低相关。
在13岁以下儿童中，给予泊沙康唑混悬液18（范围17 - 19）mg/kg/天的给药方案可使达到推荐目标浓度的儿童比例更高。多种因素对泊沙康唑谷浓度有显著影响。治疗药物监测对于识别泊沙康唑暴露不足并及时调整剂量很重要。
