Browse

A population pharmacokinetic study of intravenous busulfan in pediatric patients undergoing hematopoietic stem cell transplantation
소아 조혈모세포이식 환자에서 정맥투여 부설판의 집단약동학 연구

Cited 0 time in Web of Science Cited 0 time in Scopus
Authors
이수진
Advisor
유경상
Major
의과대학 의과학과
Issue Date
2017-08
Publisher
서울대학교 대학원
Keywords
Population pharmacokinetic modelingIntravenous busulfanPediatricOnce-daily nomogram
Description
학위논문 (박사)-- 서울대학교 대학원 의과대학 의과학과, 2017. 8. 유경상.
Abstract
Introduction: The dosage for once-daily intravenous busulfan in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) has been challenging mainly due to the high inter-individual variability of busulfan. This study was conducted to characterize the pharmacokinetics (PK) and identify significant covariates for intravenous (IV) busulfan, and to derive an optimal once-daily IV busulfan dosing nomogram for pediatric patients undergoing HSCT.
Methods: A population PK analysis was performed using 2,183 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).
Results: A one-compartment open linear PK model incorporating patients 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.
Conclusions: The once-daily busulfan dosing nomogram suggested in this study performed better than the other regimens in achieving the therapeutic target AUC, which can be useful for clinicians, particularly in a setting where TDM service is not readily available.
Language
English
URI
https://hdl.handle.net/10371/137047
Files in This Item:
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Theses (Ph.D. / Sc.D._의과학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse