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A population pharmacokinetic study of intravenous busulfan in pediatric patients undergoing hematopoietic stem cell transplantation : 소아 조혈모세포이식 환자에서 정맥투여 부설판의 집단약동학 연구
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 유경상 | - |
dc.contributor.author | 이수진 | - |
dc.date.accessioned | 2017-10-27T17:03:30Z | - |
dc.date.available | 2017-10-27T17:03:30Z | - |
dc.date.issued | 2017-08 | - |
dc.identifier.other | 000000144969 | - |
dc.identifier.uri | https://hdl.handle.net/10371/137047 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 의과대학 의과학과, 2017. 8. 유경상. | - |
dc.description.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. | - |
dc.description.tableofcontents | ABSTRACT i
CONTENTS iii LIST OF TABLES v LIST OF FIGURES vi LIST OF ABBREVIATIONS vii INTRODUCTION 1 METHODS 6 Patients and treatments 6 Population PK analysis 7 Model qualification 11 Performance comparison of busulfan dosing regimens 11 RESULTS 14 Patient demographics 14 Population PK model 16 Model qualification 20 Optimal once-daily busulfan dosing nomogram 23 Comparison of dosing regimens 25 DISCUSSION 30 REFERENCES 36 APPENDICES 46 1. Model structure for simulations 46 2. Individual fitting plots 47 3. NONMEM control for the final model 56 국문 초록 59 | - |
dc.format | application/pdf | - |
dc.format.extent | 1958504 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | Population pharmacokinetic modeling | - |
dc.subject | Intravenous busulfan | - |
dc.subject | Pediatric | - |
dc.subject | Once-daily nomogram | - |
dc.subject.ddc | 610.72 | - |
dc.title | A population pharmacokinetic study of intravenous busulfan in pediatric patients undergoing hematopoietic stem cell transplantation | - |
dc.title.alternative | 소아 조혈모세포이식 환자에서 정맥투여 부설판의 집단약동학 연구 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Su-jin Rhee | - |
dc.description.degree | Doctor | - |
dc.contributor.affiliation | 의과대학 의과학과 | - |
dc.date.awarded | 2017-08 | - |
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