Work

Optimization strategies for voriconazole dosing in pediatric populations: integrating therapeutic indications and age-stratified pharmacokinetics

Year: 2026

Type: article

Abstract: ABSTRACT There is limited evidence on the recommended voriconazole (VCZ) concentration ranges for prophylactic versus therapeutic use, and the factors influencing individualized dosing in young children remain insufficiently characterized. This retrospective study analyzed the clinical data from pediatric patients (2–17 years) at Peking University People’s Hospital from September 2020 to December 2024. The aim was to define optimal concentration thresholds for prophylaxis and treatment and identify sources of pharmacokinetic variability across age groups to support individualized dosing in children. In the exposure-effect study, VCZ trough concentration (C min ) was significantly correlated with clinical efficacy. VCZ C min ≥0.41 mg/L and C min ≥1.115 mg/L were proven to be significant predictors of prophylactic and therapeutic dosing success, respectively. For pharmacokinetic analysis, patients were stratified into three age groups: Group 1 (2 to <6 years), Group 2 (6 to <12 years), and Group 3 (≥12 years). The final multiple regression analysis showed that affecting factors, including sex, moderate-to-severe inflammation, cytochrome P450 2C19 (CYP2C19) metabolic phenotype, and coadministration, explained 34.5%, 23.4%, and 47.6% of the variability in VCZ exposure in three groups, respectively. This study investigated pediatric patients with hematologic malignancies to define exposure-response differences between therapeutic and prophylactic VCZ regimens and identify age-related determinants of exposure variability. Overall, the findings support the use of individualized, age-appropriate dosing strategies to optimize VCZ exposure in children.

Source: Antimicrobial Agents and Chemotherapy

DOI: 10.1128/aac.01169-25