Intravenous busulfan in children prior to stem cell transplantation: study of pharmacokinetics in association with early clinical outcome and toxicity.

Autor: Zwaveling, J, Bredius, R G M, Cremers, S C L M, Ball, L M, Lankester, A C, Teepe-Twiss, I M, Egeler, R M, den Hartigh, J, Vossen, J M
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Zdroj: Bone Marrow Transplantation; Jan2005, Vol. 35 Issue 1, p17-23, 7p
Abstrakt: Summary:We studied the pharmacokinetics of intravenous busulfan (Bu) in children in order to further optimize intravenous Bu dosing in relation to toxicity and survival. A total of 31 children undergoing Bu-based conditioning for allogeneic SCT were enrolled in a study. The starting dose was 1.0?mg/kg (age<4 years) and 0.8?mg/kg (age?4 years), four doses per day during 4 days. Dose adjustment was allowed up to a maximum dose of 1.0?mg/kg per dose if the target area under the serum concentration-time curve (AUC) was not reached. Pharmacokinetic studies were performed after the first dose. Donor engraftment was established in 28 out of 31 patients. The average AUC after the first dose was the same in children<4 years as in children?4 years. Mean clearance was higher in children<4 years than in children?4 years. In 35%of all patients, total AUC was within the target AUC. The other children's AUCs were below the target range. No relationships were found between systemic exposure to Bu and toxicity or clinical outcome. We concluded that, in accordance with previous data, within the observed AUCs no clear relationship was observed between Bu AUC and outcome with respect to toxicity, engraftment and relapse.Bone Marrow Transplantation (2005) 35, 17-23. doi:10.1038/sj.bmt.1704707 Published online 25 October 2004 [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index