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Evaluation of a Test Dose Strategy for Pharmacokinetically-guided Busulfan Dosing for Hematopoietic Stem Cell Transplant.

08:00 EDT 19th September 2018 | BioPortfolio

Summary of "Evaluation of a Test Dose Strategy for Pharmacokinetically-guided Busulfan Dosing for Hematopoietic Stem Cell Transplant."

Targeted busulfan dosing helps to limit chemotherapy-related toxicity and optimize disease outcomes in hematopoietic stem cell transplant (HCT). The objective of this study was to evaluate busulfan exposure from a pharmacokinetic (PK)-guided dosing strategy utilizing a test dose. This retrospective evaluation included adult patients who underwent HCT at our institution with busulfan-based myeloablative (> 9 mg/kg) conditioning from January 2014 through October 2015. A weight-based test dose of 0.8 mg/kg was used with PK assessments to predict area under the curve (AUC) achieved with weight-based dosing, with a goal AUC of 4800 µM*min (AUC). 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). A PK-guided first dose resulted in achievement of target AUC with target ranges of ±10%, ±15%, and ±20% in 50%, 75%, and 94% of patients, respectively. This was an improved rate of target achievement when compared to the 33%, 44%, and 63% of patients that achieved the desired AUC for each target range, respectively, when using weight-based dosing (p = 0.12, 0.004, and <0.001, respectively). The PK-guided strategy also decreased the variability of AUC from 3.6-fold in AUC from the weight-based test doses (2700.8 to 9631 µM*min; SD 1211.6 µM*min) to 1.8-fold in AUC from the PK-guided first doses (3672.1 to 6609.8 µM*min; SD 574.7 µM*min). 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 being within the ±10% target range (p = 0.04 for both associations). There was no significant association between AUC and death, relapse, or a composite of the two. These results show a significant improvement in target AUC attainment and less interpatient variability with PK-guided dosing utilizing a test dose strategy versus weight-based dosing.

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This article was published in the following journal.

Name: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
ISSN: 1523-6536
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