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
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
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Drug-Induced Thromboembolic Events in Patients with Malignancy
Cardiovascular & Hematological Disorders-Drug Targets Busulfan Use in Hematopoietic Stem Cell Transplantation: Pharmacology, Dose Adjustment, Safety and Efficacy in Adults and Children
Current Drug Safety The Balance between von-Willebrand Factor and its Cleaving Protease ADAMTS13: Biomarker in Systemic Inflammation and Development of Organ Failure?
Current Molecular Medicine Optimizing Conventional Medical Therapies in Inflammatory Bowel Disease in 2014
Current Drug Targets Advances in Drug Safety
Current Pharmaceutical Design Busulphan in Blood and Marrow Transplantation: Dose, Route, Frequency and Role of Therapeutic Drug Monitoring
Current Clinical Pharmacology Gynura Segetum Related Hepatic Sinusoidal Obstruction Syndrome: A Liver Disease with High Mortality and Misdiagnosis Rate
Current Pharmaceutical Design Pulmonary Hypertension and Lung Transplantation
Current Hypertension Reviews Therapeutic Use of Nitric Oxide Scavengers in Shock and Sepsis
Current Pharmaceutical Design Current and Experimental Antibody-Based Therapeutics: Insights, Breakthroughs, Setbacks and Future Directions
Current Molecular Medicine Role of Cytokines in the Pathophysiology of Acute Graft-Versus-Host Disease (GVHD)– Are Serum/Plasma Cytokines Potential Biomarkers for Diagnosis of Acute GVHD Following Allogeneic Hematopoietic Cell Transplantation (Allo-HCT)?
Current Stem Cell Research & Therapy Thiopurine Immunomodulators in Ulcerative Colitis: Moving Forward with Current Evidence
Current Drug Targets Thiopurines in Inflammatory Bowel Disease - The Role of Pharmacogenetics and Therapeutic Drug Monitoring
Current Pharmacogenomics PDE5 Inhibitor Treatment Options for Urologic and Non-Urologic Indications: 2012 Update
Current Pharmaceutical Design Monoclonal Antibodies, Bispecific Antibodies and Antibody-Drug Conjugates in Oncohematology
Recent Patents on Anti-Cancer Drug Discovery Identification of Proteins Interacting with Human SP110 During the Process of Viral Infections
Medicinal Chemistry Acute Renal Failure in Different Malignant Tumors
Current Medicinal Chemistry Pulmonary Arterial Hypertension: Need to Treat
Inflammation & Allergy - Drug Targets (Discontinued) Monoclonal Antibodies in Clinical Oncology
Anti-Cancer Agents in Medicinal Chemistry Endothelial Effects of Drugs Designed to Treat Erectile Dysfunction
Current Pharmaceutical Design