Evaluation of Limited Sampling Methods for Oral Busulfan Pharmacokinetic Monitoring in Adult Patients Undergoing Hematopoietic Stem Cell Transplantation

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Monitoring busulfan area under the plasma concentration–time curve (AUC) to establish the dose regimen for stem cell transplantation desirable to achieve efficacy while avoiding toxicity.


Our objective was to compare AUCs calculated by 18 limited sampling methods (LSMs) from 2 to 5 samples to reference AUCs determined from 10 samples in a retrospective study of 103 adult patients receiving oral busulfan. LSMs using 2 or 3 samples were ineffective.


Four LSMs using 4 or 5 blood samples that accurately characterized busulfan AUC were identified. The best 2 methods were obtained with sampling at 0.5, 1, 2, 4, and 6 hours and after 1, 1.5, 2, 4, and 6 hours postdose. For these LSMs, the incidence of 20% difference between AUCs from LSMs and reference AUCs was less than 1.3%.


Effective and safe determination of AUC for oral busulfan can be made with strategies using only 4 or 5 concentration timepoints.

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