ISSN:
1432-0843
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The pharmacokinetics of high-dose busulfan given orally at 1 mg/kg every 6 h over 4 days (total dose, 16 mg/kg) in combined chemotherapy followed by autologous bone marrow transplantation was studied in 12 children with a mean age of 7 years (range, 4–14 years). Busulfan levels in biological fluids were measured by a gas chromatographic assay with mass fragmentographic detection, using a deuterated analogue as the internal standard. In a high-dose regimen, busulfan followed one-compartment model kinetics with zero-order absorption. A mean maximal concentration of 803±228 ng/ml was achieved at 92–255 min after dosing. The mean elimination half-life was 2.33 h, and the mean total clearance was 119±54 ml/min per m2, with an apparent distribution volume of 27.10±11.50 l/m2. A mean trough level of 370 ng/ml was found throughout the 4 days of the chemotherapy course. There were no significant variations in pharmacokinetic parameters measured after the first and last doses. Busulfan was monitored in the CSF of nine children at 3.25–7 h after the last dose and was detected in all patients, with a mean CSF-to-plasma concentration ratio of 0.95 (range, 0.5–1.4).
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00257448
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