title: Modeling the effect of succimer (DMSA; dimercaptosuccinic acid) chelation therapy in patients poisoned by lead.
abstract: BACKGROUND
  Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer (dimercaptosuccinic acid; DMSA) chelation therapy on blood lead concentrations.
  
  
  METHODS
  We integrated a two-compartment kinetic succimer model into an existing PBPK lead model and produced a Chelation Lead Therapy (CLT) model. The accuracy of the model's predictions was assessed by simulating clinical observations in patients poisoned by lead and treated with succimer. The CLT model calculates blood lead concentrations as the sum of the background exposure and the acute or chronic lead poisoning. The latter was due either to ingestion of traditional remedies or occupational exposure to lead-polluted ambient air. The exposure duration was known. The blood lead concentrations predicted by the CLT model were compared to the measured blood lead concentrations.
  
  
  RESULTS
  Pre-chelation blood lead concentrations ranged between 99 and 150 μg/dL. The model was able to simulate accurately the blood lead concentrations during and after succimer treatment. The pattern of urine lead excretion was successfully predicted in some patients, while poorly predicted in others.
  
  
  CONCLUSIONS
  Our model is able to predict blood lead concentrations after succimer therapy, at least, in situations where the duration of lead exposure is known.
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 City Hospital , National Poisons Information Service (Birmingham Unit) , Birmingham , UK.|e School of Biosciences , University of Birmingham , Birmingham , UK.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Bradberry
authors.affiliation: d City Hospital , National Poisons Information Service (Birmingham Unit) , 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: f ScitoVation , Research Triangle Park , Durham, NC , USA.
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Clewell
authors.affiliation: b National Poisons Information Center, University Medical Center Utrecht , Utrecht , The Netherlands.|g Department of Intensive Care Medicine , University Medical Center Utrecht , Utrecht , The Netherlands.|h 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: D000293:Adolescent; D000328:Adult; D000931:Antidotes / Q000627:therapeutic use; D002614:Chelating Agents / Q000627:therapeutic use*; D015913:Chelation Therapy / Q000379:methods; D006801:Humans; D007854:Lead / Q000097:blood / Q000652:urine; D007855:Lead Poisoning / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008519:Medicine, Traditional / Q000009:adverse effects; D008954:Models, Biological; D016273:Occupational Exposure / Q000009:adverse effects; D015203:Reproducibility of Results; D004113:Succimer / Q000627:therapeutic use*
chemical_list: D000931:Antidotes; D002614:Chelating Agents; D007854:Lead; D004113:Succimer
keywords: Chelation; DMSA; PBK model; chelation lead therapy model; dimercaptosuccinic acid; intoxication; lead; poisoning; succimer