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

## TL;DR

This study identifies optimal voriconazole concentration thresholds and factors affecting dosing in children, supporting personalized treatment strategies based on age and other variables.

## Contribution

The study provides age-stratified pharmacokinetic insights and defines distinct concentration thresholds for prophylactic and therapeutic use of voriconazole in pediatric patients.

## Key findings

- Voriconazole trough concentrations of ≥0.41 mg/L and ≥1.115 mg/L are significant for prophylactic and therapeutic success, respectively.
- Age, sex, inflammation, CYP2C19 metabolism, and drug interactions explain variability in voriconazole exposure across pediatric age groups.
- The study supports individualized dosing strategies to optimize voriconazole exposure in children with hematologic malignancies.

## 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 (Cmin) was significantly correlated with clinical efficacy. VCZ Cmin ≥0.41 mg/L and Cmin ≥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.