Abstract
Busulfan is the only agent used in myeloablative regimens for hematopoietic stem cell transplantation for which therapeutic drug monitoring (TDM) has been widely used. Studies of oral busulfan (Bu) indicate wide intrapatient and interpatient variations in pharmacokinetic (PK) behavior, particularly in children. Dose adjustments of oral Bu based on TDM to bring exposures within established therapeutic ranges have been shown to reduce toxicity and improve outcomes. Intravenous (IV) Bu is becoming more widely used and has much more predictable PK. Outcomes with IV Bu appear to be superior to those achieved using oral Bu without TDM. However there is still at least a threefold variation in exposures achieved by the same dose of IV Bu in different individuals and a small proportion of patients will experience toxic exposures with current dosing regimens. Therapeutic monitoring with appropriate dose adjustment is therefore recommended for all patients treated with regimens containing high doses of Bu. Giving IV Bu at a fixed rate to adults will narrow the range of exposures but more work is needed to establish the best dosing regimen to bring as many exposures as possible within the target range. Studies of test dosing of IV Bu show that this strategy is more accurate when test and treatment doses are infused at the same rate. Finally, targeting exposures to the upper end of the therapeutic range may provide a safe approach to exploiting dose-intensity for the treatment of some malignancies.
Keywords: Busulfan, hematopoietic stem cell (HSCs), therapeutic drug monitoring (TDM), Intravenous (IV) Bu, malignancies
Current Pharmaceutical Design
Title: Therapeutic Drug Monitoring of Busulfan in Transplantation
Volume: 14 Issue: 20
Author(s): J. A. Russell and S. B. Kangarloo
Affiliation:
Keywords: Busulfan, hematopoietic stem cell (HSCs), therapeutic drug monitoring (TDM), Intravenous (IV) Bu, malignancies
Abstract: Busulfan is the only agent used in myeloablative regimens for hematopoietic stem cell transplantation for which therapeutic drug monitoring (TDM) has been widely used. Studies of oral busulfan (Bu) indicate wide intrapatient and interpatient variations in pharmacokinetic (PK) behavior, particularly in children. Dose adjustments of oral Bu based on TDM to bring exposures within established therapeutic ranges have been shown to reduce toxicity and improve outcomes. Intravenous (IV) Bu is becoming more widely used and has much more predictable PK. Outcomes with IV Bu appear to be superior to those achieved using oral Bu without TDM. However there is still at least a threefold variation in exposures achieved by the same dose of IV Bu in different individuals and a small proportion of patients will experience toxic exposures with current dosing regimens. Therapeutic monitoring with appropriate dose adjustment is therefore recommended for all patients treated with regimens containing high doses of Bu. Giving IV Bu at a fixed rate to adults will narrow the range of exposures but more work is needed to establish the best dosing regimen to bring as many exposures as possible within the target range. Studies of test dosing of IV Bu show that this strategy is more accurate when test and treatment doses are infused at the same rate. Finally, targeting exposures to the upper end of the therapeutic range may provide a safe approach to exploiting dose-intensity for the treatment of some malignancies.
Export Options
About this article
Cite this article as:
Russell A. J. and Kangarloo B. S., Therapeutic Drug Monitoring of Busulfan in Transplantation, Current Pharmaceutical Design 2008; 14 (20) . https://dx.doi.org/10.2174/138161208785061382
DOI https://dx.doi.org/10.2174/138161208785061382 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
?Revolutionizing Cancer Treatment: Nano-Therapeutics Targeting Tumor Microenvironment?
This thematic issue explores the forefront of cancer treatment, centering on the groundbreaking potential of nano-therapeutics meticulously designed to target the tumor microenvironment. At its core, the issue aims to unravel the latest advancements in nanotechnology, showcasing innovative materials, formulations, and delivery systems that hold promise for redefining cancer therapeutics. ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Pulmonary Arterial Hypertension in HIV-infected Patients
Current Hypertension Reviews Phosphodiesterase 5 Inhibitors in the Treatment of Erectile Dysfunction
Current Pharmaceutical Design Treatment of Acute Leukaemias with Monoclonal Antibodies: Current Status and Future Prospects
Cardiovascular & Hematological Agents in Medicinal Chemistry Can Antidiabetic Drugs Improve Male Reproductive (Dys)Function Associated with Diabetes?
Current Medicinal Chemistry Recent Advancements in Diagnosis and Therapy of Liver Cirrhosis
Current Drug Targets Plasminogen Activator Inhibitor-1 in Vascular Thrombosis
Current Drug Targets Intravenous Immunoglobulin Preparations and Autoimmune Disorders: Mechanisms of Action
Current Pharmaceutical Biotechnology Effect of an Angiotensin II Receptor Blocker and Two Angiotensin Converting Enzyme Inhibitors on Transforming Growth Factor-β (TGF-β) and α-Actomyosin (α SMA), Important Mediators of Radiation-Induced Pneumopathy and Lung Fibrosis
Current Pharmaceutical Design Pulmonary Hypertension: Current Therapy and Future Prospects
Cardiovascular & Hematological Agents in Medicinal Chemistry Novel and Emerging Drugs for Acute Lymphoblastic Leukemia
Current Cancer Drug Targets Pyrrolizidine Alkaloids and their Biological Properties from Indian Heliotropium Species
Current Bioactive Compounds Microvascular Diseases: Is A New Era Coming?
Cardiovascular & Hematological Agents in Medicinal Chemistry Current and Experimental Antibody-Based Therapeutics: Insights, Breakthroughs, Setbacks and Future Directions
Current Molecular Medicine Therapeutic Hypothermia in Brain Injuries and Related Diseases
Recent Patents on Inflammation & Allergy Drug Discovery Monoclonal Antibodies in Clinical Oncology
Anti-Cancer Agents in Medicinal Chemistry Old Drugs-Current Perspectives
Current Pharmacogenomics Pharmacogenetics of Childhood Acute Lymphoblastic Leukemia
Current Pharmacogenomics Therapeutic Use of Nitric Oxide Scavengers in Shock and Sepsis
Current Pharmaceutical Design Metabolic Syndrome and Non-Cardiac Vascular Diseases: An Update from Human Studies
Current Pharmaceutical Design Monoclonal Antibody Therapy in Haematological Malignancies
Current Clinical Pharmacology