Pharmacokinetics of a test dose of Intravenous busulfan guide dose modifications to achieve an optimal area under the curve of a single daily dose of intravenous busulfan in children undergoing a reduced-intensity conditioning regimen with hematopoietic stem cell transplantation

Morris Kletzel*, David Jacobsohn, Reggie E Duerst

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

We studied 30 pediatric patients with malignant (n = 16) or nonmalignant (n = 14) conditions. The preparative regimen consisted of fludarabine, intravenous (IV) busulfan (Bu) for 2 daily doses, and antithymocyte globulin before stem cell transplantation. A test dose of IV Bu (0.8 mg/ kg), anticipated to target an area under the concentration-time curve (AUC) of 800 to 1200 μmol · min, was followed later by 2 daily doses adjusted according to the pharmacokinetics (PK) to target an AUC of 3200 to 4800 μmol · min. The median test dose AUC was 953 μmol · min (range, 439-1315 μmol · min). The median AUC of single daily doses was 3798 μmol niddot; min (range, 1511-7254 μmol · min). PK-based dose modification was required in 20 patients: 12 were adjusted to a higher dose, and in 8 the dose was decreased. Nausea and vomiting were noted in 15 patients. No patient developed hepatic veno-occlusive disease or seizures. Full donor chimerism was attained in 20 patients (mean of 24.5 days), 3 achieved partial chimerism, 5 did not engraft, and in 2 it is too early to assess chimerism. Acute graft-versus-host disease developed in 11 patients, grades I to II developed in 10 patients, and grade III developed in 1. Four patients died of infection and 5 of progressive disease. Thus, PK of a test dose of IV Bu provided information to adjust subsequent daily doses of IV Bu: this resulted in a regimen that was feasible, safe, and convenient for administration to children.

Original languageEnglish (US)
Pages (from-to)472-479
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume12
Issue number4
DOIs
StatePublished - Apr 2006

Funding

We thank Kimberly Thorman, Kelly Coyne, Mary Stoelinga, and Theresa Morrison, the nurses of the Ambulatory Stem Cell Unit and the Oncology Unit (4 West), and Marvin M. Goldenberg (editorial review). This work was supported by a restricted grant from ESP Pharmaceuticals, Inc. None of the authors has a financial interest in ESP Pharmaceuticals, Inc., whose product, IV Busulfex, was studied in this work.

Keywords

  • Busulfan/fludarabine
  • Hematopoietic stem cell transplantation
  • Pediatrics
  • Pharmacokinetics
  • Single-dose daily regimen

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Fingerprint

Dive into the research topics of 'Pharmacokinetics of a test dose of Intravenous busulfan guide dose modifications to achieve an optimal area under the curve of a single daily dose of intravenous busulfan in children undergoing a reduced-intensity conditioning regimen with hematopoietic stem cell transplantation'. Together they form a unique fingerprint.

Cite this