College of Pharmacy, Daegu Catholic University, Gyeongsan, 38430, Republic of Korea.
College of Pharmacy, Wonkwang University, Iksan, 54538, Republic of Korea.
Drug Des Devel Ther. 2024 Mar 20;18:871-879. doi: 10.2147/DDDT.S451970. eCollection 2024.
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.
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.
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.
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.
接受造血干细胞移植的儿科患者接受静脉注射白消安作为预处理方案。白消安的每日一次方案被提议作为传统方案的更方便的替代方案，但它可能会增加毒性的风险，如静脉阻塞性疾病（VOD）。本研究旨在评估每日一次方案的药代动力学（PKs），并研究适当的静脉输注时间以降低毒性风险。
回顾并选择了儿科患者的每日一次白消安给药方案，包括基于 EMA 和 FDA 的每日一次给药方案。我们使用先前开发的群体 PK 模型生成了虚拟儿科患者的白消安 PK 数据。PK 曲线和达到参考最大浓度（Cmax）的患者比例以及白消安的暴露情况用于评估两种输注时间和给药方案的适宜性。
预测的 PK 曲线和白消安的暴露情况显示，所有每日一次的给药方案都具有相对相似的分布。当所有每日一次的方案应用 3 小时输注时，大多数患者可能超过参考 Cmax，这可能与 VOD 的高风险相关。
虽然静脉注射每日一次的白消安通常输注 3 小时，但我们的研究结果强调需要考虑足够的输注时间，以确保安全用药并预防毒性，这将有助于儿科肿瘤学中白消安的最佳使用。
