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• W2600486518 abstract "Busulfan, a bifunctional alkylating agent, has been used as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to derive a novel once-daily intravenous (IV) busulfan dosing nomogram for pediatric patients undergoing HSCT using a population pharmacokinetic (PK) model. A population PK analysis was performed using 2183 busulfan concentrations in 137 pediatric patients (age: 0.6-22.2 years), who received IV busulfan once-daily for 4 days before undergoing HSCT. Based on the final population PK model, an optimal once-daily IV busulfan dosing nomogram was derived. The percentage of simulated patients achieving the daily target area under the concentration-time curve (AUC) by the new nomogram was compared with that by other busulfan dosing regimens including the FDA regimen, the EMA regimen, and the empirical once-daily regimen without therapeutic drug monitoring (TDM). A one-compartment open linear PK model incorporating patient's body surface area, age, dosing day, and aspartate aminotransferase as a significant covariate adequately described the concentration-time profiles of busulfan. An optimal dosing nomogram based on the PK model performed significantly better than the other dosing regimens, resulting in >60% of patients achieving the target AUC while the percentage of patients exceeding the toxic AUC level was kept <25% during the entire treatment period. A novel once-daily busulfan dosing nomogram for pediatric patients undergoing HSCT is useful for clinicians, particularly in a setting where TDM service is not readily available or to optimize the dose on day 1." @default.
• W2600486518 created "2017-04-07" @default.
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• W2600486518 date "2017-05-30" @default.
• W2600486518 modified "2023-10-03" @default.
• W2600486518 title "Pediatric patients undergoing hematopoietic stem cell transplantation can greatly benefit from a novel once-daily intravenous busulfan dosing nomogram" @default.
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• W2600486518 doi "https://doi.org/10.1002/ajh.24734" @default.
• W2600486518 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28370238" @default.
• W2600486518 hasPublicationYear "2017" @default.
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