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Evaluation of a Test Dose Strategy for Pharmacokinetically-Guided Busulfan Dosing for Hematopoietic Stem Cell Transplantation.
- Source :
-
Biology of Blood & Marrow Transplantation . Feb2019, Vol. 25 Issue 2, p391-397. 7p. - Publication Year :
- 2019
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Abstract
- Highlights • Using a busulfan test dose and pharmacokinetic (PK)-guided dosing improves target area under the curve (AUC) attainment. • PK-guided dosing achieved target AUC in more patients compared with weight-based dosing. • There was less interpatient variability in AUC with PK-guided dosing. • Confirmatory first-dose PK analysis is necessary to adjust busulfan doses. • No associations between busulfan AUC and toxicity, death, or relapse were identified. ABSTRACT Targeted busulfan dosing helps limit chemotherapy-related toxicity and optimize disease outcomes in hematopoietic stem cell transplantation (HCT). The objective of this study was to evaluate busulfan exposure from a pharmacokinetic (PK)-guided dosing strategy using a test dose. This retrospective evaluation included adult patients who underwent HCT at our institution with busulfan-based myeloablative (>9 mg/kg) conditioning between January 2014 and October 2015. A weight-based test dose of 0.8 mg/kg was used with PK assessments to predict area under the curve (AUC pred) achieved with weight-based dosing, with a target AUC of 4800 µM*minute (AUC target). PK from the test dose was then used to calculate a PK-guided first myeloablative busulfan dose. PK assessments were also done after the first dose to assess if the goal area under the curve (AUC) had been achieved (AUC first). A PK-guided first dose resulted in achievement of target AUC with target ranges of ±10% in 50% of patients, ±15% in 75%, and ±20% in 94%. This was an improved rate of target achievement compared with the 33%, 44%, and 63% of patients who achieved the desired AUC for these respective target ranges when using weight-based dosing (P =.12,.004, and <.001, respectively). The PK-guided strategy also decreased the variability of AUC from 3.6-fold in AUC pred from the weight-based test doses (2700.8 to 9631 µM*minute; SD, 1211.6 µM*minute) to 1.8-fold in AUC first from the PK-guided first doses (3672.1 to 6609.8 µM*minute; SD, 574.7 µM*minute). This reflects a 2-fold improvement in AUC variability with a PK-guided dosing strategy. This is also improved from the 3-fold variability in AUC reported in other studies. Weight and body surface area were significantly associated with the likelihood of AUC first being within the ±10% target range (P =.04 for both associations). There was no significant association between AUC first and death, relapse, or a composite of the two. These results demonstrate a significant improvement in target AUC attainment and less interpatient variability with PK-guided dosing using a test dose strategy compared with weight-based dosing. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10838791
- Volume :
- 25
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Biology of Blood & Marrow Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 134152420
- Full Text :
- https://doi.org/10.1016/j.bbmt.2018.09.017