Intra-individual Pharmacokinetic Variability of Intravenous Busulfan in Hematopoietic Stem Cell-Transplanted Children.

Clinical Pharmacokinetics
Hanen MarsitSylvain Goutelle

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

Jan 1, 1993·Cancer Chemotherapy and Pharmacology·M HassanM Lindgren
Jun 21, 2007·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Jeannine S McCuneGeorge B McDonald
Jul 7, 2011·The Annals of Pharmacotherapy·Alison M GulbisBorje S Andersson
Jul 9, 2011·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Rosa F YehJeannine S McCune
Sep 16, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mirjam N TrameGeorg Hempel
Nov 13, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jeannine S McCuneNicholas H G Holford
May 9, 2014·European Journal of Clinical Pharmacology·Christian DiestelhorstGeorg Hempel
Aug 3, 2016·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Jeanne PalmerPaul A Carpenter
Aug 3, 2017·Expert Opinion on Drug Metabolism & Toxicology·Alan L MyersBorje S Andersson
Sep 1, 2017·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Karen SweissPritesh Patel

❮ Previous
Next ❯

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.

Related Papers

Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses
A S O'Marcaigh, D L Betcher
Expert Opinion on Drug Metabolism & Toxicology
Jeannine S McCune, Leona A Holmberg
Hoja tisiológica
R J Pintos Fuentes, N Reissenweber
© 2021 Meta ULC. All rights reserved