Trough level monitoring of intravenous busulfan to estimate the area under the plasma drug concentration–time curve in pediatric hematopoietic stem cell transplant recipients

Optimizing systemic busulfan exposure, the area under the concentration–time curve (AUC), improves the outcomes for hematopoietic stem cell transplantation (HSCT). The AUC is conventionally calculated using six plasma concentrations (AUC 0–∞ ) drawn after the first of 16 intravenous busulfan doses g...

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Bibliographic Details
Published in:International journal of hematology 2015-11, Vol.102 (5), p.611-616
Main Authors: Watanabe, Erika, Nishikawa, Takuro, Ikawa, Kazuro, Yamaguchi, Hiroki, Abematsu, Takanari, Nakagawa, Shunsuke, Kurauchi, Koichiro, Kodama, Yuichi, Tanabe, Takayuki, Shinkoda, Yuichi, Matsumoto, Kazuaki, Okamoto, Yasuhiro, Takeda, Yasuo, Kawano, Yoshifumi
Format: Article
Language:English
Subjects:
Adolescent
Allografts
Area Under Curve
Busulfan - administration & dosage
Busulfan - pharmacokinetics
Child
Child, Preschool
Disease-Free Survival
Female
Hematology
Hematopoietic Stem Cell Transplantation
Humans
Infant
Male
Medicine
Medicine & Public Health
Monitoring, Physiologic
Neoplasms - blood
Neoplasms - mortality
Neoplasms - therapy
Oncology
Original Article
Survival Rate
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Summary:Optimizing systemic busulfan exposure, the area under the concentration–time curve (AUC), improves the outcomes for hematopoietic stem cell transplantation (HSCT). The AUC is conventionally calculated using six plasma concentrations (AUC 0–∞ ) drawn after the first of 16 intravenous busulfan doses given as a 2-h infusion every 6 h. The aim of the present study was to develop limited sampling strategies using three or fewer busulfan concentrations to reliably calculate AUC 0–∞ in patients undergoing HSCT. We investigated the pharmacokinetics of busulfan 46 times in 29 pediatric patients receiving intravenous busulfan. Limited sampling strategies using one, two, or three plasma busulfan concentrations were developed by multiple linear regression that showed excellent agreement with AUC 0–∞ . In single-point sampling strategies, the AUC 0–∞ predicted based on C 6 (trough level: busulfan plasma concentration 6 h after the start of the infusion) was significantly correlated with, and not statistically different from, actual values as follows: AUC 0–∞  = 2556.5 C 6  + 320.9 ( r 2  = 0.929, P  
ISSN:0925-5710
1865-3774
DOI:10.1007/s12185-015-1853-6