A population pharmacokinetic study of fludarabine in paediatric patients undergoing haematopoietic stem cell transplantation

Abstract

Introduction: Fludarabine is used as a common component of conditioning regimens for haematopoietic stem cell transplantation (HSCT). However, knowledge regarding the pharmacokinetic characteristics of once-daily fludarabine dosing in children is limited. This study investigated the pharmacokinetics of fludarabine and explored its associations with clinical outcomes in paediatric patients.<br/> <br/> Methods: A total of 802 concentration data obtained from 43 paediatric patients who underwent HSCT and administered fludarabine were included in a population pharmacokinetic analysis using non-linear mixed-effects modelling. Based on individual systemic exposures derived from the model, associations between F-ara-A exposure and clinical outcome variables were explored.<br/> <br/> Results: A two-compartment model with proportional residual error adequately described the concentration-time profile of F-ara-A. The body surface area (BSA) and glomerular filtration rate were significant covariates for the clearance of F-ara-A. No significant associations were found between systemic exposure and graft-versus-host disease, relapse or survival.<br/> <br/> Conclusion: This study evaluated the pharmacokinetics of F-ara-A after fludarabine administration in paediatric patients. Comparable systemic exposure to that of previous reports from adults may support the appropriateness of BSA-based dosing in children.<br/>