Drug Design, Development and Therapy (Mar 2024)
Optimal Once-Daily Busulfan Administration in Pediatric Patients: A Simulation-Based Investigation of Intravenous Infusion Times
Abstract
Yun Kim,1 Sungha Moon,2 Su-Jin Rhee2 1College of Pharmacy, Daegu Catholic University, Gyeongsan, 38430, Republic of Korea; 2College of Pharmacy, Wonkwang University, Iksan, 54538, Republic of KoreaCorrespondence: Su-Jin Rhee, College of Pharmacy, Wonkwang University, Iksan, 54538, Republic of Korea, Tel +82-63-850-6822, Email [email protected]: Pediatric patients receiving hematopoietic stem cell transplantation undergo regular administration of intravenous busulfan as a conditioning regimen. Once-daily regimen of busulfan has been proposed as a more convenient alternative to the traditional regimen, but it may increase the risk of toxicity such as veno-occlusive disease (VOD). The study aims to evaluate the pharmacokinetics (PKs) of once-daily regimens and investigate appropriate intravenous infusion times to reduce the risk of toxicity.Patients and methods: Once-daily busulfan dosing regimens for pediatric patient were reviewed and selected including EMA- and FDA-based once-daily dosing regimens. We generated busulfan PK data of virtual pediatric patients using a previously developed population PK model. PK profiles and proportion of patients achieving the referenced maximum concentration (Cmax) and exposure to busulfan were used to evaluate the appropriateness of both infusion time and dosing regimens.Results: Predicted PK profiles and exposure of busulfan showed relatively similar distributions for all once-daily dosing regimens. Most patients exceeded the referenced Cmax possibly associated with a high risk of VOD with all once-daily regimens when applied with 3 hours of infusion.Conclusion: While intravenous infusion of once-daily busulfan is typically administered over 3 hours, our findings emphasize the necessity of considering sufficient infusion times to ensure safe drug utilization and prevent toxicity, which will aid in optimal busulfan use in pediatric oncology.Keywords: busulfan, pediatrics, population pharmacokinetics, once-daily dosing regimen, infusion times
