|
|
 Previous Article | Table of Contents | Next Article 
Busulfan disposition in children
LB Grochow, W Krivit, CB Whitley and B Blazar
Division of Pharmacology and Experimental Therapeutics, Johns Hopkins
Oncology Center, Baltimore, MD 21205.
Children receive busulfan orally as part of myeloablative therapy before
bone marrow transplantation for malignant and nonmalignant conditions.
Children have been reported to have a low incidence of severe toxicity and
significant rates of failure to achieve full engraftment. We evaluated the
disposition of busulfan in children between 2 months and 3.6 years of age
with lysosomal storage diseases, leukemia, and immunodeficiency disorders
receiving oral doses of 1 or 2 mg/kg using a gas chromatographic assay.
Peak concentrations were lower than those previously reported for adults,
ranging from 1.4 to 5.2 mumol/L. The harmonic mean of the elimination
half-life was 92 minutes, which is only slightly faster than that for
adults (140 minutes). However, the area under the curve ranged from 400 to
1,000 (715 +/- 240) mumol.min/L, substantially lower than in adults
receiving 1 mg/kg (range, 710 to 5,100 mumol.min/L; mean +/- SD, 2,180 +/-
1,200). The apparent volume of distribution (assuming complete
bioavailability) ranged from 0.28 to 3.53 L/kg (1.42 +/- 0.86), which is
more than twice that reported for adults (0.60 +/- 0.42). Busulfan
clearance rate normalized to surface area is twice as high in children (200
+/- 100 mL/min/m2) as it is in adults (95 +/- 54 mL/min/m2). Alterations in
bioavailability (absorption or first pass elimination) or in actual volume
of distribution may account for these differences in drug disposition. The
observed differences suggest the need for separate phase I dose escalation
studies in children with accompanying pharmacokinetic assessment.
Volume 75,
Issue 8,
pp. 1723-1727,
04/15/1990
Copyright © 1990 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. P. Booth, A. Rahman, R. Dagher, D. Griebel, S. Lennon, D. Fuller, C. Sahajwalla, M. Mehta, and J. V. S. Gobburu
Population Pharmacokinetic-Based Dosing of Intravenous Busulfan in Pediatric Patients
J. Clin. Pharmacol.,
January 1, 2007;
47(1):
101 - 111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Gibbs, C. A. Liacouras, R. N. Baldassano, and J. T. Slattery
Up-Regulation of Glutathione S-Transferase Activity in Enterocytes of Young Children
Drug Metab. Dispos.,
December 1, 1999;
27(12):
1466 - 1469.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
W.-K. Lai, C.-P. Pang, L.-K. Law, R. Wong, C.-K. Li, and P. M.-P. Yuen
Routine analysis of plasma busulfan by gas chromatography–mass fragmentography
Clin. Chem.,
December 1, 1998;
44(12):
2506 - 2510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Peters, E. G. Shapiro, J. Anderson, P. J. Henslee-Downey, M. R. Klemperer, M. J. Cowan, E. F. Saunders, P. A. deAlarcon, C. Twist, J. B. Nachman, et al.
Hurler Syndrome: II. Outcome of HLA-Genotypically Identical Sibling and HLA-Haploidentical Related Donor Bone Marrow Transplantation in Fifty-Four Children
Blood,
April 1, 1998;
91(7):
2601 - 2608.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. O'Marcaigh and D. L. Betcher
Busulfan
Journal of Pediatric Oncology Nursing,
January 1, 1996;
13(3):
150 - 152.
[PDF]
|
|
|
|
|
