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Pharmacokinetics of intravenous busulfan in children prior to stem cell transplantation
Author(s) -
Cremers Serge,
Schoemaker Rik,
Bredius Robbert,
Den Hartigh Jan,
Ball Lynne,
Twiss Irene,
Vermeij Pieter,
Vossen Jaak
Publication year - 2002
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2002.01555.x
Subject(s) - busulfan , pharmacokinetics , medicine , transplantation , regimen , population , pharmacology , surgery , hematopoietic stem cell transplantation , environmental health
Aims Intravenous formulations of busulfan have recently become available. Although busulfan is used frequently in children as part of a myeloablative regimen prior to bone marrow transplantation, pharmacokinetic data on intravenous busulfan in children are scarce. The aim was to investigate intravenous busulfan pharmacokinetics in children and to suggest a limited sampling strategy in order to determine busulfan systemic exposure with the minimum of inconvenience and risk for the patient. Methods Plasma pharmacokinetics after the first administration was investigated in six children using nonlinear mixed effect modelling. Results Pharmacokinetics showed little variability and were described adequately with a one‐compartment model (population estimates CL,av=0.29 l h −1 kg −1 ; V ,av=0.84 l kg −1 ; t 1/2 =1.7–2.8 h). Combined with limited sampling and a Bayesian fitting procedure, the model can adequately estimate the systemic exposure to intravenous busulfan, which in children appears to be at the lower end of the adult range. Conclusions Busulfan systemic exposure in children during intravenous administration can be estimated adequately with limited sampling and a Bayesian fitting procedure from a one‐compartment model. Intravenous busulfan pharmacokinetics in children should be the subject of more research.