title: Busulfan.
abstract: OBJECTIVE
  To review the current published studies evaluating the pharmacokinetics, clinical efficacy, safety, and toxicity of busulfan in pediatric and adult patients.
  
  
  METHODS
  English-language literature published between 1953 and 1993 was analyzed; pertinent literature was reviewed.
  
  
  METHODS
  Emphasis was placed on pharmacologic studies and clinical trials involving busulfan therapy both in myeloproliferative disorders and in conditioning regimens for autologous or allogeneic bone marrow transplantation.
  
  
  METHODS
  Data from both pediatric and adult studies were evaluated; emphasis was placed on the relationship between plasma concentrations of busulfan and its efficacy and toxicity.
  
  
  RESULTS
  Busulfan has been used widely at conventional dosages (1-12 mg/d) for the treatment of patients with chronic myelogenous leukemia (CML). Busulfan at high doses (usually 16 mg/kg) given with other cytotoxic drugs (especially cyclophosphamide) is a common preparative regimen in patients undergoing allogeneic or autologous bone marrow transplantation (BMT) for acute or chronic leukemia and other nonmalignant disorders (e.g., hemoglobinopathies, inborn error of immune system, congenital metabolic disorders). Pharmacokinetics of high-dose busulfan are age-dependent. Busulfan systemic exposure and, thus, tissue and tumor exposure are lower in children than with adults. Relationships between toxicity (principally neutropenia, hepatic veno-occlusive disease, incidence of seizures) and drug exposure were found for busulfan.
  
  
  CONCLUSIONS
  Busulfan is a useful, sufficiently safe drug in the treatment of patients with CML. At higher dosages, busulfan is a fundamental part of myeloablative therapies for patients undergoing BMT. As the pharmacokinetics and metabolism of busulfan is further understood, there is great potential for improving treatment outcome. An assessment of maximal tolerated exposure determined by therapeutic drug monitoring may decrease the incidence and lethality of regimen-related toxicities.
authors: Department of Pharmacology, Istitato di Ricovero e Cura a Carattere Scientifico, Policlinico S. Matteo, Pavia, Italy.
authors: I
authors: I
authors: Buggia
authors: F
authors: F
authors: Locatelli
authors: M B
authors: MB
authors: Regazzi
authors: M
authors: M
authors: Zecca
mesh_terms: D000367:Age Factors; D001798:Blood Proteins / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D009196:Myeloproliferative Disorders / Q000188:drug therapy; D011485:Protein Binding; D015203:Reproducibility of Results
chemical_list: D001798:Blood Proteins; D002066:Busulfan