PIII‐45

BACKGROUND Conditioning regimens preceding stem cell transplant (SCT) often include oral busulfan, and may be complicated by hepatic veno‐occlusive disease (HVOD). IV busulfan (IV Bu) causes less HVOD in adults. We describe the pharmacokinetics (PK) of IV Bu in infants and children, determine its incidence and correlate IV Bu AUC with its development. METHODS 24 children who underwent SCT. Initial IV Bu doses were based on patient weight. 7 blood samples were drawn after the first dose. PK parameters were calculated using 1‐compartment analysis (WinNonLin 4.1). The third and subsequent doses were adjusted to achieve an AUC of 900–1500μMol·min. RESULTS Patient age range was 3mo‐16.9yrs (9 infants). Mean IV Bu PK parameters were: Cmax=4.7±0.9μMol; Vss=0.70±0.22L/kg; ke=0.005±0.001min −1 ; AUC=1256±320μMol·min. Mean IV Bu AUC of infants was not different from older children (1164μ±331Mol·min vs. 1311±311μMol·min; p=0.35). The mean Vss was higher in infants (0.84±0.29L/kg vs. 0.62±0.10L/kg; p=0.025), but the mean clearance was not different. HVOD was diagnosed in 6 patients(25%), including 3 infants. 5 patients had moderate HVOD and1 had fatal HVOD. Mean IV Bu AUC was 1317±310μMol·min and 1074±299μMol·min in the non‐HVOD vs. the HVOD group, respectively (p=0.10). CONCLUSIONS Busulfan Vss differs significantly between infants and older children. No association was observed between IV Bu AUC and the development of HVOD in children where busulfan doses are adjusted to achieve a target IV Bu AUC. Clinical Pharmacology & Therapeutics (2005) 79 , P70–P70; doi: 10.1016/j.clpt.2005.12.253