Therapeutic drug monitoring of posaconazole for effective prophylaxis of invasive fungal infections in pediatric patients: A pilot study

Abstract

Introduction: Posaconazole, a second-generation triazole agent, is a drug with wide interindividual variation in bioavailability and variability of pharmacokinetics. The European Conference on Infections in Leukemia recommends the implementation of posaconazole therapeutic drug monitoring (TDM) in children to provide certainty regarding the efficacy of treatment and to increase its safety. A concentration of posaconazole in plasma in prophylactic regimens of above 0.7 mg/L is recommended. The aim of our pilot study was to discover the most effective method of posaconazole plasma concentration measurement, and to analyze posaconazole pharmacokinetics profiles in pediatric patients on posaconazole prophylaxis. Material and methods: Children receiving oncological treatment or hematopoietic stem cell transplantation in the Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology in Wroclaw Medical University Hospital were included in the trial. Posaconazole concentration was determined at the MonitLabTM laboratory using a newly validated high-performance liquid chromatography with fluorescence detector method. Results: Initial analysis shows that the major problem in patients on antifungal prophylaxis is inadequately low plasma drug concentration. Conclusions: Clinical trials on TDM of posaconazole should be developed.