Accurate targeting of daily intravenous busulfan with 8-hour blood sampling in hospitalized adult hematopoietic cell transplant recipients.

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2012
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Abstract
Daily intravenous (i.v.) busulfan is increasingly being used in hematopoietic cell transplantation (HCT) conditioning regimens. Intravenous busulfan doses administered at the traditional frequency of every 6 hours can be targeted ((T)Bu) to a patient-specific concentration at steady state (C(ss)) using therapeutic drug monitoring (TDM). In this report, we describe our experiences with TDM of daily i.v. busulfan in an adult population, with the specific aims of (1) evaluating covariates associated with busulfan clearance, and (2) assessing the feasibility of TDM for outpatient administration of daily (T)Bu with pharmacokinetic sampling over 6 hours. A retrospective pharmacokinetic analysis was conducted in 87 adults receiving daily (T)Bu as part of cyclophosphamide followed by (T)BU (CY/(T)BU), fludarabine monophosphate (fludarabine) followed by (T)BU, or (T)BU concurrent with fludarabine conditioning. The desired C(ss) was achieved in 85% of patients receiving daily i.v. busulfan. Busulfan clearance was not associated with sex or age, but was associated with the day of dosing and conditioning regimen (P = .0016). In patients receiving CY/(T)BU, no differences in clearance were found between dosing days (P > .36); however, clearance decreased significantly in patients receiving fludarabine-based regimens (P = .0016). Busulfan clearance and C(ss) estimates from pharmacokinetic sampling over 8, 11, or 24 hours were comparable (P > .4). However, pharmacokinetic modeling of individual patient concentration-time data over 6 hours could not reliably estimate busulfan clearance or C(ss).
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yeh2012accuratebiology Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Yeh, Rosa F;Pawlikowski, Matthew A;Blough, David K;McDonald, George B;O'Donnell, Paul V;Rezvani, Andrew;Deeg, H Joachim;McCune, Jeannine S;
Journal biology of blood and marrow transplantation : journal of the american society for blood and marrow transplantation
Year 2012
DOI 10.1016/j.bbmt.2011.06.013
URL
Keywords
therapeutic drug monitoring transplantation kidney pharmacokinetics liver tacrolimus algorithm mycophenolic acid dose ciclosporin equation immunosuppressive drugs

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