Modeling the effect of succimer (DMSA; dimercaptosuccinic acid) chelation therapy in patients poisoned by lead

J.C.H. Eijkeren, J. Daniël N Olie, Sally M Bradberry, J Allister Vale, I de Vries, HJ 3rd Clewell, J Meulenbelt, CC Hunault

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

CONTEXT: 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.

MATERIALS AND 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.

Original languageEnglish
Pages (from-to)133-141
Number of pages9
JournalClinical Toxicology
Volume55
Issue number2
DOIs
Publication statusPublished - Feb 2017

Keywords

  • Adolescent
  • Adult
  • Antidotes
  • Chelating Agents
  • Chelation Therapy
  • Humans
  • Lead
  • Lead Poisoning
  • Male
  • Medicine, Traditional
  • Models, Biological
  • Occupational Exposure
  • Reproducibility of Results
  • Succimer

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