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Pharmacokinetics of once-daily IV busulfan as part of pretransplantation preparative regimens: a comparison with an every 6-hour dosing schedule.

Authors :
Madden T
de Lima M
Thapar N
Nguyen J
Roberson S
Couriel D
Pierre B
Shpall EJ
Jones RB
Champlin RE
Andersson BS
Source :
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2007 Jan; Vol. 13 (1), pp. 56-64.
Publication Year :
2007

Abstract

In pretransplantation therapy busulfan is typically given every 6 hours. We infused busulfan once daily at 130 mg/m2 for 4 days, performing pharmacokinetic analyses on plasma concentration-time data (n = 60 patients) on days 1, 3, and/or 4. Mean (percent coefficient of variation) maximum concentration, volume of distribution, half-life, and clearance were 3.6 microg/mL (13.8%), 22.6 L/m2 (20.2%), 2.73 hours (27.5%), and 109 mL/min/m2 (26%), respectively. The mean (percent coefficient of variation) and median daily areas under the curve were 4873 (21.8%) and 4871 microM x minute. Intrapatient variability in day-to-day estimated clearance was <20%, without day-to-day drug accumulation. The pharmokinetic parameters were compared with those from 47 patients given intravenous busulfan at approximately 0.8 mg/kg (approximately 32 mg/m2) every 6 hours. We conclude that there is (1) a dose proportionality based on mean and median areas under the curve, (2) unchanged estimated clearance with a 4-fold increase in dose and a 2.5-fold difference in dosing rate, (3) negligible variability in dose-to-dose pharmacokinetics and negligible interdose accumulation with once-daily administration, and (4) no change in pharmokinetic parameter(s) with concomitant use of imidazole antifungals, oral contraceptives, or phenytoin. In summary, intravenous busulfan has highly predictable, linear pharmacokinetics from 32 mg/m2 (approximately 0.8 mg/kg) to 130 mg/m2 (approximately 3.2 mg/kg). Further, once-daily intravenous busulfan dosing is convenient, favoring its more widespread application.

Details

Language :
English
ISSN :
1083-8791
Volume :
13
Issue :
1
Database :
MEDLINE
Journal :
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
Publication Type :
Academic Journal
Accession number :
17222753
Full Text :
https://doi.org/10.1016/j.bbmt.2006.08.037