Disposition of high-dose busulfan in pediatric patients undergoing bone marrow transplantation

Autor: I. Buggia, Mario Regazzi, Silvana Quaglini, Federico Bonetti, Massimo Pregnolato, Franco Locatelli, Marco Zecca
Rok vydání: 1993
Předmět:
Zdroj: Clinical pharmacology and therapeutics. 54(1)
ISSN: 0009-9236
Popis: We studied the pharmacokinetics of busulfan (16 mg/kg) in 16 pediatric patients affected by malignant and nonmalignant disorders between 6 months and 19 years of age (mean ± SD, 5.7 ± 6.5 years) who were undergoing allogeneic (15 patients) and autologous (one patient) bone marrow transplantation. In all children, the conditioning regimen consisted of busulfan given orally at a dose of 1 mg/kg every 6 hours for 16 doses (total dose, 16 mg/kg), associated with other drugs. The pharmacokinetics of busulfan was studied during the 6-hour dosing interval on the third day of therapy by use of a high-performance liquid chromatographie assay. The value for the time to reach maximum concentration, expressed as mean ± SD, was 1.1 ± 0.5 hour; maximum concentration was 609.6 ± 225.3 ng/ml; steady-state concentration was 358.9 ± 135.5 ng/ml; area under the plasma concentration–time curve was 2153.6 ± 813.1 ng · hr/ml; oral clearance was 0.535 ± 0.226 L/hr/kg; and half-life was 2.4 ± 0.8 hours. Age-related differences in busulfan disposition were observed. The mean busulfan oral clearance in a group of 10 patients with an age range from 6 months to 3 years was 0.619 L/hr/kg, whereas six patients whose ages ranged from 7 to 19 years had a oral clearance of 0.396 L/hr/kg. The half-lives for busulfan during infancy decrease continuously until early childhood but were prolonged in older children. No significant relationship between systemic exposure to busulfan and drug effect was observed. Clinical Pharmacology and Therapeutics (1993) 54, 45–52; doi:10.1038/clpt.1993.108
Databáze: OpenAIRE
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