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Busulfan bioavailability
M Hassan, P Ljungman, P Bolme, O Ringden, Z Syruckova, A Bekassy, J Stary, I Wallin and N Kallberg
Research Department, Huddinge Hospital, Stockholm, Sweden.
Busulfan is widely used as a component of the myeloablative therapy in bone
marrow transplantation. Recent studies have shown that the drug disposition
is altered in children and is associated with less therapeutic
effectiveness, lower toxicities, and higher rates of engraftment failure.
We have evaluated the bioavailability of the drug in two groups of
patients: eight children between 1.5 and 6 years of age and eight older
children and adults between 13 and 60 years. Oral bioavailability showed a
large interindividual variation. In children, the bioavailability ranged
from 0.22 to 1.20, and for adults, it was within the range 0.47 to 1.03.
The elimination half-life after intravenous administration in children
(2.46 +/- 0.27 hours; mean +/- SD) did not differ from that obtained for
adults (2.61 +/- 0.62 hours). However, busulfan clearance normalized to
body weight was significantly higher in children (3.62 +/- 0.78
mL.min-1.kg-1) than that in adults (2.49 +/- 0.52 mL.min-1.kg-1). Also, the
distribution volume normalized for body weight was significantly higher in
children (0.74 +/- 0.10 L.kg-1) compared with 0.56 +/- 0.10 L. kg-1 in
adults. The difference in clearance between children and adults was not
statistically significant when normalized to body surface area, which most
probably shows that busulfan dosage should be calculated on the basis of
surface area rather than body weight. However, to avoid drug-related
toxicities, drug monitoring and an individual dose adjustment should be
considered because of the variability in busulfan bioavailability.
Volume 84,
Issue 7,
pp. 2144-2150,
10/01/1994
Copyright © 1994 by The American Society of Hematology
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