Intra-individual Pharmacokinetic Variability of Intravenous Busulfan in Hematopoietic Stem Cell-Transplanted Children.
Abstract
Busulfan therapeutic drug monitoring (TDM) is necessary to better achieve the target exposure in children before hematopoietic stem cell transplantation (HSCT). However, TDM-based dosing may be challenging if intra-individual pharmacokinetic variability (also denoted inter-occasion variability [IOV]) occurs during therapy. The objectives of this study were to describe and quantify busulfan IOV in children, and to investigate its potential determinants. We performed a new analysis of published data from children who received intravenous busulfan over 4 days before HSCT. We calculated individual pharmacokinetic parameters on each day of therapy using a published population pharmacokinetic model of busulfan and analyzed their changes. Population estimation of IOV was also performed with non-linear mixed effects (NLME) modeling. Potential predictors of significant decrease in busulfan clearance (CL) were assessed by using machine learning approaches. IOV could be assessed in 136 children. Between day (D) 1 and D2, most patients (80%) experienced a decrease in busulfan CL, with a median change of - 7.9%. However, both large decreases (minimum, - 48.5%) and increases in CL (maximum, + 44%) were observed. Over D1-D3 of therapy, mean ...Continue Reading
References
Citations
Related Concepts
Related Feeds
Blood And Marrow Transplantation
The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.
Allogenic & Autologous Therapies
Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.