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. 2002 Apr;53(4):386-9.
doi: 10.1046/j.1365-2125.2002.01555.x.

Pharmacokinetics of intravenous busulfan in children prior to stem cell transplantation

Serge Cremers  1 , Rik Schoemaker, Robbert Bredius, Jan den Hartigh, Lynne Ball, Irene Twiss, Pieter Vermeij, Jaak Vossen
Affiliations

Pharmacokinetics of intravenous busulfan in children prior to stem cell transplantation

Serge Cremers et al. Br J Clin Pharmacol. 2002 Apr.

Abstract

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.

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Figures

Figure 1
Figure 1
Bayesian estimates of AUCs following intravenous busulphan (y axis) vs simulated AUCs (x axis). Bayesian estimates were based on the concentrations at t = 2.5 and 4 h (a) and t = 2.5 and 6 h (b) after dosing.
See this image and copyright information in PMC

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