title: Pharmacokinetics of intravenous busulfan in children prior to stem cell transplantation.
abstract: OBJECTIVE
  Intravenous formulations of busulfan have recently become available. Although busulfan is used frequently in children as part of a myeloablative regimen prior to bone marrow transplantation, pharmacokinetic data on intravenous busulfan in children are scarce. The aim was to investigate intravenous busulfan pharmacokinetics in children and to suggest a limited sampling strategy in order to determine busulfan systemic exposure with the minimum of inconvenience and risk for the patient.
  
  
  METHODS
  Plasma pharmacokinetics after the first administration was investigated in six children using nonlinear mixed effect modelling.
  
  
  RESULTS
  Pharmacokinetics showed little variability and were described adequately with a one-compartment model (population estimates CL,av=0.29 l h(-1) kg(-1); V,av=0.84 l kg(-1); t(1/2)=1.7-2.8 h). Combined with limited sampling and a Bayesian fitting procedure, the model can adequately estimate the systemic exposure to intravenous busulfan, which in children appears to be at the lower end of the adult range.
  
  
  CONCLUSIONS
  Busulfan systemic exposure in children during intravenous administration can be estimated adequately with limited sampling and a Bayesian fitting procedure from a one-compartment model. Intravenous busulfan pharmacokinetics in children should be the subject of more research.
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. S.C.L.M.Cremers@lumc.nl
authors.forename: Serge
authors.initials: S
authors.lastname: Cremers
authors.forename: Rik
authors.initials: R
authors.lastname: Schoemaker
authors.forename: Robbert
authors.initials: R
authors.lastname: Bredius
authors.forename: Jan
authors.initials: J
authors.lastname: den Hartigh
authors.forename: Lynne
authors.initials: L
authors.lastname: Ball
authors.forename: Irene
authors.initials: I
authors.lastname: Twiss
authors.forename: Pieter
authors.initials: P
authors.lastname: Vermeij
authors.forename: Jaak
authors.initials: J
authors.lastname: Vossen
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D001499:Bayes Theorem; D002066:Busulfan / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D006207:Half-Life; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007223:Infant; D007275:Injections, Intravenous; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000628:therapy; D013789:Thalassemia / Q000097:blood / Q000628:therapy; D019172:Transplantation Conditioning
chemical_list: D007166:Immunosuppressive Agents; D002066:Busulfan