Therapeutic Drug Monitoring of Voriconazole in Children from a Tertiary Care Center in China.

Abstract

Voriconazole is a broad-spectrum triazole antifungal and the first-line treatment for invasive aspergillosis (IA). The aim of this research was to study the dose adjustments of voriconazole as well as the affecting factors influencing voriconazole trough concentrations in Asian children to optimize its daily administration. Clinical data were analyzed of inpatients 2 to 14 years old who were subjected to voriconazole trough concentration monitoring from 1 June 2015 to 1 December 2017. A total of 138 voriconazole trough concentrations from 42 pediatric patients were included. Voriconazole trough concentrations at steady state ranged from 0.02 to 9.35 mg/liter, with high inter- and intraindividual variability. Only 50.0% of children achieved the target range (1.0 to 5.5 mg/liter) at initial dosing, while 35.7% of children were subtherapeutic, and 14.3% of children were supratherapeutic at initial dosing. There was no correlation between initial trough concentrations and initial dosing. A total of 28.6% of children (12/42) received an adjusted dose according to trough concentrations. Children <6, 6 to 12, and >12 years old required a median oral maintenance dose to achieve the target range of 11.1, 7.2, and 5.3 mg/kg twice daily, respectively (P = 0.043). The average doses required to achieved the target range were 7.7 mg/kg and 5.6 mg/kg, respectively, and were lower than the recommended dosage (P = 0.033 and 0.003, respectively). Affecting factors such as administration routes and coadministration with proton pump inhibitors (PPIs) explained 55.3% of the variability in voriconazole exposure. Therapeutic drug monitoring (TDM) of voriconazole could help to individualize antifungal therapy for children and provide guidelines for TDM and dosing optimization in Asian children.