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Pharmacokinetics analysis results are similar for oral compared to intravenous busulfan in patients undergoing hematopoietic stem cell transplantation, except for the earlier onset of mucositis. A controlled clinical study

Bone Marrow Transplantation volume 54, pages 1799–1804 (2019)Cite this article

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Abstract

Busulfan is used in myeloablative schemes for hematopoietic stem cell transplantation (HSCT), with monitoring of dosage through the area under the curve (AUC) of the drug plasma concentration (µMol min). In this study, we compared the complete pharmacokinetics of busulfan administered orally (Bu-Oral) and intravenously (Bu-IV). We evaluated 40 patients who underwent HSCT with different types of conditioning regimens. After one dose, in the Bu-Oral group (n = 21), the median AUC was 1174 µMol min (799–4000), reaching a median of 4440 µMol min (3428–7181.5) during conditioning in 24 h. In the Bu-IV group (n = 19), it was 1244.8 µMol min (1001.2–2021), reaching 5598.0 µMol min (3102–8818) during conditioning in 24 h. Measuring plasma concentration of Bu in patients undergoing HSCT is important, regardless of the formulation, and the inclusion of a pre-HSCT test can predict the optimal dose during conditioning. Pharmacokinetics of the oral administration of busulfan, as well as clearance, are extremely variable, and this can potentially compromise the clinical results of the treatment since it makes it difficult to predict clinical results.

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Acknowledgments

The authors wish to thank the Brazilian Ministry of Health for the financial assistance for this study. IA, FRK and NH designed the study, collected and interpreted data and wrote the manuscript. FPSS, AAFR, AS, EKS, JJNK, JCB, JSRO, and JFF collected and interpreted data and reviewed the manuscript critically. BA and MDL interpreted study data and reviewed the manuscript critically. All authors reviewed and approved the final version to be published.

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Authors and Affiliations

  1. Oncology and Hematology Center, Hospital Israelita Albert Einstein, São Paulo, Brazil

    Iracema Esteves

  2. Department of Bone Marrow Transplantation, Hospital Israelita Albert Einstein, São Paulo, Brazil

    Fabio Pires Souza Santos

  3. Bone Marrow Transplantation Unit, Itaci Hospital, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil

    Juliana Folloni Fernandes

  4. Hospital Samaritano, São Paulo, Brazil

    Adriana Seber

  5. Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil

    José Salvador Rodrigues Oliveira

  6. Hematology and Bone Marrow Transplantation Centers, Albert Einstein Hospital, São Paulo, Brazil

    Nelson Hamerschlak

  7. Hematology and Hemotherapy Department, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil

    Fabio Rodrigues Kerbauy

  8. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Borje S. Andersson

  9. Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, USA

    Marcos de Lima

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  1. Iracema Esteves
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Correspondence to Iracema Esteves.

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Paper presented in the ASH and EBMT events in 2016.

This controlled clinical study was registered in the Clinicaltrials.gov database (Protocol NCT 01800643)

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Esteves, I., Santos, F.P.S., Fernandes, J.F. et al. Pharmacokinetics analysis results are similar for oral compared to intravenous busulfan in patients undergoing hematopoietic stem cell transplantation, except for the earlier onset of mucositis. A controlled clinical study. Bone Marrow Transplant 54, 1799–1804 (2019). https://doi.org/10.1038/s41409-019-0521-5

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