The impact of hemodialysis on the clearance of busulfan was determined in a patient with chronic renal failure undergoing autologous peripheral stem cell transplantation for non-Hodgkin's lymphoma. The extraction ratio for busulfan across the dialyzer was 0.530 +/- 0.026 at a blood flow of 400 ml/min, which corresponds to a hemodialysis clearance of 2.23 +/- 0.11 ml/min/kg body weight. Apparent oral clearance of busulfan without hemodialysis was 3.38 +/- 0.56 ml/min/kg. Thus, a 4 h hemodialysis session enhanced the apparent oral clearance of busulfan by 65%. We conclude that hemodialysis effectively removes busulfan from circulating blood, but a standard hemodialysis period (ie, 4 h) does not significantly alter busulfan exposure. Bone Marrow Transplantation(2000) 25, 201-203.
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http://dx.doi.org/10.1038/sj.bmt.1702112 | DOI Listing |
Chemotherapy
November 2024
Service and Laboratory of Clinical Pharmacology, Department of Internal Medicine and Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Background: Despite major advances in cancer treatment in the past years, there is a need to optimize chemotherapeutic drug dosing strategies to reduce toxicities, suboptimal responses, and the risk of relapse. Most cancer drugs have a narrow therapeutic index with substantial pharmacokinetics variability. Yet, current dosing approaches do not fully account for the complex pathophysiological characteristics of the patients.
View Article and Find Full Text PDFJCI Insight
October 2024
Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, Department of Obstetrics, Obstetrics and Gynaecology Center, The First Hospital of Jilin University, Changchun, China.
Ther Drug Monit
May 2024
Laboratoire de Pharmacologie, Oncopole Claudius-Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Centre de Recherche en Cancérologie de Toulouse, INSERM U1037, Université Paul Sabatier, Toulouse, France.
Background: Conditioning bifunctional agent, busulfan, is commonly used on children before hematopoietic stem cell transplantation. Currently, at the Ramathibodi hospital, Bangkok, Thailand, initial dosing is calculated according to age and body surface area, and 7 samples per day are used for therapeutic drug monitoring (TDM). This study aimed to identify the best strategies for individual dosages a priori from patient characteristics and a posteriori based on TDM.
View Article and Find Full Text PDFJ Pharmacokinet Pharmacodyn
June 2024
InsightRX, 548 Market St. #88083, San Francisco, CA, 94104, USA.
Dose personalization improves patient outcomes for many drugs with a narrow therapeutic index and high inter-individuality variability, including busulfan. Non-compartmental analysis (NCA) and model-based methods like maximum a posteriori Bayesian (MAP) approaches are two methods routinely used for dose optimization. These approaches vary in how they estimate patient-specific pharmacokinetic parameters to inform a dose and the impact of these differences is not well-understood.
View Article and Find Full Text PDFPharmaceutics
December 2023
Department of Stem Cell Transplantation, University Children's Hospital Zurich-Eleonore Foundation & Children's Research Center (CRC), University of Zurich, 8032 Zurich, Switzerland.
Reaching target exposure of busulfan-based conditioning prior to hematopoietic stem cell transplantation is vital for favorable therapy outcomes. Yet, a wide inter-patient and inter-occasion variability in busulfan exposure has been reported, especially in children. We aimed to identify factors associated with the variability of busulfan pharmacokinetics in 124 consecutive patients transplanted at the University Children's Hospital Zurich between October 2010 and February 2020.
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