A Perspective Study on Therapeutic Drug Monitoring of Voriconazole in Pediatric Patients with Hematologic Disorders

Abstract

Background: The incidence of invasive aspergillosis and the administration of voriconazole have risen among immunocompromised patients. Objectives: This study aimed to evaluate serum voriconazole concentration and its corresponding influential factors in pediatric patients with hematologic disorders. Methods: A total of 132 blood samples were collected from 44 pediatric patients with hematologic disorders infected with invasive aspergillosis and treated with voriconazole. Among these patients, 20.5% were classified as having proven invasive aspergillosis, 77.2% as probable, and 2.3% as possible. Voriconazole serum levels were evaluated using HPLC on the 3rd, 5th, and 7th days of treatment. Genotyping of the CYP2C19 alleles (*2, *3, and *17) was performed, and demographic and clinical data were gathered from records between 2018 to 2020. Results: The voriconazole concentration in 70.5% of patients and 77.3% of treatment cases (complete or partial) ranged from 1 to 5.5 µg/mL. Adverse events were observed in 4.5% of the patients. Genotyping of CYP2C19 genes revealed CYP2C1911 (5.4%), CYP2C19117 (16.2%), CYP2C1912 (51.4%), and CYP2C19217 (27%). Multivariate analysis using linear regression demonstrated that serum voriconazole concentration increased by 0.037 µg/mL per year of age and by 0.06 µg/mL for each unit increase in C-reactive protein (on the 3rd day of voriconazole therapy). Additionally, an increase in alanine aminotransferase level by 1 unit decreased the mean voriconazole concentration by 0.03 µg/mL. Of these patients, 65.9% were completely treated, 11.4% were partially treated, and 22.7% died. Conclusions: Serum voriconazole concentrations varied among pediatric hematologic patients receiving standard doses, with age, C-reactive protein, and alanine aminotransferase levels affecting the concentration of voriconazole in the sera of pediatric patients.