title: Prospective pharmacokinetic study of intravenous busulfan in hematopoietic stem cell transplantation in 25 children.
abstract: The aim of this study was to prospectively evaluate the PK and safety of ivBU in 25 Japanese children (median age six yr; range, five months-17 yr) as one of a combination of drugs in a pretransplant regimen. The patients had acute leukemia (n = 14), CML (2), JMML (5), solid tumors (2), chronic granulomatous disease (1), or metachromatic leukodystrophy (1). Five different dose schedules were used according to the patient's ABW: <9 kg (1.0 mg/kg), 9 to <16 (1.2 mg/kg), 16-23 (1.1 mg/kg), >23-34 (0.95 mg/kg), and >34 kg of BW (0.8 mg/kg). Each dose was given over two h, and sample blood was drawn at nine or 11 separate points for analysis by gas chromatography-mass spectrometry. The AUC varied from 796 to 1905 μmol min/L, and 19 of the 25 patients (76%) remained within the target range without dose adjustment. Two were diagnosed with engraftment failure. Hepatic VOD developed in four, and only one of these showed high AUC (>1500 μmol min/L). Toxicities did not correlate with the BU level. Our data showed very similar PK to those in previous studies, and these dose schedules are applicable to Japanese children.
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Yasuhiro
authors: Y
authors: Okamoto
authors: Yoshihisa
authors: Y
authors: Nagatoshi
authors: Yoshiyuki
authors: Y
authors: Kosaka
authors: Akira
authors: A
authors: Kikuchi
authors: Shunichi
authors: S
authors: Kato
authors: Hisato
authors: H
authors: Kigasawa
authors: Yasuo
authors: Y
authors: Horikoshi
authors: Megumi
authors: M
authors: Oda
authors: Makoto
authors: M
authors: Kaneda
authors: Tetsuya
authors: T
authors: Mori
authors: Hideo
authors: H
authors: Mugishima
authors: Masahiro
authors: M
authors: Tsuchida
authors: Shuichi
authors: S
authors: Taniguchi
authors: Yoshifumi
authors: Y
authors: Kawano
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D044466:Asian People; D002066:Busulfan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007564:Japan; D008297:Male; D019653:Myeloablative Agonists / Q000493:pharmacokinetics; D011446:Prospective Studies; D019172:Transplantation Conditioning
chemical_list: D019653:Myeloablative Agonists; D002066:Busulfan
keywords: adverse events; area under the curve; busulfan; children