Possibly Appropriate Maintenance dose of Voriconazole in pediatric patients: a single center observational study

Abstract Background: Voriconazole is a triazole antifungal agent and a commonly used first-line treatment for invasive aspergillosis (IA). The study was performed to explore the factors affecting voriconazole trough concentration and maintenance dose to optimize voriconazole dosage in pediatric patients. Method: The demographic information, concentration data, CYP2C19 genotypes, and clinical outcomes of eligible pediatric patients from January 1th, 2016 to December 31th, 2018 were collected retrospective . Result: The study finally included 145 voriconazole trough concentrations from 94 pediatric patients. Steady trough concentration ranged from 0.04 to 16.11 μg/mL. Morerover, the distinction between the maximum and the minimum corrected concentration of per kilogram maintenance dosage is as high as 907 folds and children ≤2 years old showed the minimum variation compared to other individuals (P<0.001). A high inter- and intra-individual variability of voriconazole in pediatric patients were observed. Only 54.5% of the pediatric patients achieved the target range (1.0 to 5.5 μg/mL) at unadjusted initial dosage, while 35.9% of children were subtherapeutic, only 9.6% of children were supratherapeutic at unadjusted initial dosing. The younger children (≤12 years) seem to have a lower trough concentration (P=0.0096) and lower percentage of target achievements (P=0.004). And 98.97% of the maintenance dosage was below 9.0 mg/kg. For pediatric patients of different ages, it was found that most of them was underdosed. While, to achieve targeted therapeutic level for different age groups of ≤2, 2-6, 6-12, and 12-18 years, the median voriconazole maintenance doses were 5.7, 6.7, 5.0, and 3.3 mg-1kg/12h, respectively had been required in order to achieve therapeutic level (P<0.001). Conclusion: Pediatric patients especially those ≤12 years old might need a higher dosage regime to achieve therapeutic trough concentration. Importantly, early and repeat monitoring of voriconazole is essential to ensure the effectiveness and safety of voriconazole in children.