BUSULFAN PHARMACOKINETICS USING A SINGLE DAILY HIGH-DOSE REGIMEN IN CHILDREN WITH ACUTE-LEUKEMIA

The pharmacokinetics of busulfan, given as a single daily dose (either 4 mg/kg or 150 mg/m(2)), was determined in 22 children undergoing bon e marrow transplantation for acute leukemia. The single daily dose reg imen showed similar pharmacokinetics to previously reported regimens o f 4 x 1 mg/kg, except for fourfold higher mean peak plasma levels and negligible trough levels. Daily systemic exposure for single dose regi mens based on weight (4 mg/kg) or surface area (150 mg/m(2)), respecti vely were very similar to regimens of (4 x 1 mg/kg) or (4 x 37.5 mg/m( 2)). Dose (milligrams per kilogram), peak plasma level, and area under the curve (AUC) were all higher in 12 children treated with 150 mg/m( 2) busulfan than in 9 children treated with 4 mg/kg. AUC was age depen dent for the 4 mg/kg dose but not for the 150 mg/m(2) dose. The use of a 150 mg/m(2) dose allows escalation of the dose above 4 mg/kg, elimi nating the tendency for younger children to receive lower systemic exp osure. Little toxicity was observed in this study. Clearance and distr ibution volume correlated negatively with age, and AUC correlated posi tively with dose (milligram per kilogram). Administration of busulfan as crushed rather than whole tablets reduced the delay time for appear ance of busulfan in plasma but had no effect on absorption or other ph armacokinetic parameters. (C) 1994 by The American Society of Hematolo gy.