title: Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans.
abstract: BACKGROUND
  No kinetic models presently exist which simulate the effect of chelation therapy on lead blood concentrations in lead poisoning.
  
  
  OBJECTIVE
  Our aim was to develop a kinetic model that describes the kinetics of dimercaptosuccinic acid (DMSA; succimer), a commonly used chelating agent, that could be used in developing a lead chelating model.
  
  
  METHODS
  This was a kinetic modelling study. We used a two-compartment model, with a non-systemic gastrointestinal compartment (gut lumen) and the whole body as one systemic compartment. The only data available from the literature were used to calibrate the unknown model parameters. The calibrated model was then validated by comparing its predictions with measured data from three different experimental human studies.
  
  
  RESULTS
  The model predicted total DMSA plasma and urine concentrations measured in three healthy volunteers after ingestion of DMSA 10 mg/kg. The model was then validated by using data from three other published studies; it predicted concentrations within a factor of two, representing inter-human variability.
  
  
  CONCLUSIONS
  A simple kinetic model simulating the kinetics of DMSA in humans has been developed and validated. The interest of this model lies in the future potential to use it to predict blood lead concentrations in lead-poisoned patients treated with DMSA.
authors.affiliation: a National Institute for Public Health and the Environment , Bilthoven , The Netherlands.
authors.forename: Jan C H
authors.initials: JC
authors.lastname: van Eijkeren
authors.affiliation: b National Poisons Information Center, University Medical Center Utrecht , Utrecht , The Netherlands.|c Department of Pharmacology and Toxicology , University of Nijmegen , Nijmegen , The Netherlands.
authors.forename: J Daniël N
authors.initials: JD
authors.lastname: Olie
authors.affiliation: d National Poisons Information Service (Birmingham Unit), City Hospital , Birmingham , UK.|e School of Biosciences, University of Birmingham , Birmingham , UK.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Bradberry
authors.affiliation: d National Poisons Information Service (Birmingham Unit), City Hospital , Birmingham , UK.|e School of Biosciences, University of Birmingham , Birmingham , UK.
authors.forename: J Allister
authors.initials: JA
authors.lastname: Vale
authors.affiliation: b National Poisons Information Center, University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: Irma
authors.initials: I
authors.lastname: de Vries
authors.affiliation: b National Poisons Information Center, University Medical Center Utrecht , Utrecht , The Netherlands.|f Department of Intensive Care Medicine , University Medical Center Utrecht , Utrecht , The Netherlands.|g Institute for Risk Assessment Sciences (IRAS), Utrecht University , Utrecht , The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Meulenbelt
authors.affiliation: b National Poisons Information Center, University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: Claudine C
authors.initials: CC
authors.lastname: Hunault
mesh_terms: D000328:Adult; D002614:Chelating Agents / Q000493:pharmacokinetics*; D015913:Chelation Therapy / Q000379:methods; D006801:Humans; D007854:Lead / Q000097:blood; D007855:Lead Poisoning / Q000188:drug therapy*; D008297:Male; D008954:Models, Biological; D004113:Succimer / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D002614:Chelating Agents; D007854:Lead; D004113:Succimer
keywords: DMSA; chelation; kinetics; modelling; succimer