Evaluation of Plasma Concentration and Hepatotoxicity of Voriconazole in Pediatric Patients following Hematopoietic Stem Cell Transplantation

Background: Invasive fungal infection is one of the most important causes of morbidity and mortality in pediatric patients undergoing Hematopoietic stem cell transplantation (HSCT). Voriconazole as a broad-spectrum anti-fungal agent which has been used widely for prevention and treatment of invasive fungal infections in immunocompromised patients. Alteration in voriconazole plasma concentrations may be resulted in lack of efficacy and some adverse effects.Methods: This observational cohort study assessed the therapeutic plasma concentration of voriconazole and its relationship with hepatotoxic adverse effect in pediatric patients undergoing HSCT. Plasma concentration of voriconazole was measured by High-performance liquid chromatography (HPLC) assay with technique extracted from Khoschsorur et al.Results: Among a total of 14 pediatric patients,5 patients received voriconazole orally and 9 patients received voriconazole intravenously. The median plasma concentration of voriconazole was 1.8 mcg/ml (range, 0.75-5.54 mcg/ml). There was no correlation between voriconazole dose and plasma concentration of voriconazole(p=0.166). Trough concentration of ≥ 4 mcg/ml was observed in 2 of 3 patients who experienced severe hepatic dysfunction. The plasma concentration of voriconazole did not significantly differ in patients with or without hepatotoxicity(p=0.406).Conclusions: Our study showed that trough levels of voriconazole were sub-therapeutic in 21.4% of children. Furthermore, hepatic enzyme abnormalities were observed in half of pediatric patients following voriconazole initiation during hospitalization. We didn’t find any correlation between plasma concentration of voriconazole and the incidence of hepatotoxicity. We also didn’t observe any correlation between voriconazole dose and plasma concentration of voriconazole, but the correlation was linear after exclusion of outlier data.