Therapeutic monitoring of busulfan in pediatric bone marrow transplantation

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 (A UC) within the "therapeutic window" of 1000-1200 muM x 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 muM x min) was different (p = .006) from that after the first dose (1 mg/kg) (687.63 +/- 166.43 muM x 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.