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 (AUC) within the "therapeutic window" of 1,000-1,200 microM 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 microM x min) was different (p = .006)from that after the first dose (1 mg/kg) (687.63 +/- 166.43 microM 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.
Krivoy
N
N
Department of Medicine B, Rambam Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel. N_Krivoy@rambam.health.gov.il
Hoffer
E
E
Tabak
A
A
Elhasid
R
R
Arush
M Weyl Ben
MW
Stein
J
J
Yaniv
I
I
Rowe
J M
JM
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007223:Infant; D011446:Prospective Studies; D014018:Tissue Distribution
D018906:Antineoplastic Agents, Alkylating; D002066:Busulfan