Therapeutic monitoring of busulfan in pediatric bone marrow transplantation

N. Krivoy, E. Hoffer, A. Tabak, R. Elhasid, M. Weyl Ben Arush, J. Stein, I. Yaniv, J. M. Rowe

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this study was to describe busulfan disposition in a pediatric population who underwent bone marrow transplantation (BMT). Busulfan administered dose was 1 mg/kg every 6 h for 4 days. Plasma determinations were performed after the first dosing at 0, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min. A noncompartment analysis model for extravascular absorption was used for the pharmacokinetic analysis. To obtain the area under the concentration-time curve (AUC) within the "therapeutic window" of 1000-1200 μM × minutes a busulfan dose adjustment was performed at the fourth dose. Forty-five busulfan pharmacokinetic analyses were performed in 34 children. Eleven children had their dose adjusted [1.19 (±0.14) mg/kg/ at the fourth dose and the AUC was monitored at the fifth one. The mean AUC ± SD after the fifth dose (998.1 ± 189.2 μM × min) was different (p = .006) from that after the first dose (1 mg/kg) (687.63 ± 166.43 μM × min). Six children had their first AUC into the "therapeutic window," 17 children had their dose adjusted [1.2 (±0.22) mg/kg], but the "adjusted" AUC was not available. These data suggest that it may be reasonable to recommend a busulfan dose of 1.2 mg/kg to achieve the accepted therapeutic target in children undergoing BMT.

Original languageEnglish
Pages (from-to)31-37
Number of pages7
JournalPediatric Hematology and Oncology
Volume19
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Bone marrow transplantation
  • Busulfan
  • Children
  • Dose adjustment

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