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PJ Shaw, CE Scharping, RJ Brian and JW Earl
Department of Biochemistry, Royal Alexandra Hospital for Children,
Camperdown, Australia.
The pharmacokinetics of busulfan, given as a single daily dose (either 4
mg/kg or 150 mg/m2), was determined in 22 children undergoing bone marrow
transplantation for acute leukemia. The single daily dose regimen showed
similar pharmacokinetics to previously reported regimens of 4 x 1 mg/kg,
except for fourfold higher mean peak plasma levels and negligible trough
levels. Daily systemic exposure for single dose regimens based on weight (4
mg/kg) or surface area (150 mg/m2), respectively were very similar to
regimens of (4 x 1 mg/kg) or (4 x 37.5 mg/m2). Dose (milligrams per
kilogram), peak plasma level, and area under the curve (AUC) were all
higher in 12 children treated with 150 mg/m2 busulfan than in 9 children
treated with 4 mg/kg. AUC was age dependent for the 4 mg/kg dose but not
for the 150 mg/m2 dose. The use of a 150 mg/m2 dose allows escalation of
the dose above 4 mg/kg, eliminating the tendency for younger children to
receive lower systemic exposure. Little toxicity was observed in this
study. Clearance and distribution volume correlated negatively with age,
and AUC correlated positively with dose (milligram per kilogram).
Administration of busulfan as crushed rather than whole tablets reduced the
delay time for appearance of busulfan in plasma but had no effect on
absorption or other pharmacokinetic parameters.
This article has been cited by other articles:
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| Copyright © 1994 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
