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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.
- 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.
- Subjects :
- Acute Disease
Administration, Oral
Adolescent
Adult
Aged
Area Under Curve
Busulfan blood
Drug Administration Schedule
Drug Interactions
Female
Hematopoietic Stem Cell Transplantation methods
Humans
Infusions, Intravenous
Leukemia, Myeloid therapy
Male
Metabolic Clearance Rate
Middle Aged
Myeloablative Agonists blood
Myelodysplastic Syndromes therapy
Busulfan administration & dosage
Busulfan pharmacokinetics
Myeloablative Agonists administration & dosage
Myeloablative Agonists pharmacokinetics
Transplantation Conditioning methods
Subjects
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