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Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans
Jan C H van Eijkeren1, J Daniël N Olie2,3, Sally M Bradberry4,5
1a National Institute for Public Health and the Environment , Bilthoven , The Netherlands.
Clinical Toxicology (Philadelphia, Pa.)
|October 7, 2016
Summary
A new kinetic model simulates dimercaptosuccinic acid (DMSA) kinetics in humans. This validated model may predict blood lead levels in lead poisoning patients undergoing chelation therapy.
Area of Science:
- Pharmacokinetics
- Toxicology
- Mathematical Modeling
Background:
- Existing kinetic models do not simulate chelation therapy's impact on lead blood concentrations.
- Lead poisoning remains a significant public health concern requiring effective treatment strategies.
Purpose of the Study:
- To develop a kinetic model for dimercaptosuccinic acid (DMSA; succimer) pharmacokinetics.
- To establish a foundation for a lead chelation therapy model.
Main Methods:
- A two-compartment kinetic model was developed (gastrointestinal and systemic).
- Model parameters were calibrated using existing literature data.
- Model predictions were validated against three independent human studies.
Main Results:
- The model accurately predicted DMSA plasma and urine concentrations in healthy volunteers.
- Validation against published data showed predictions within a factor of two, accounting for inter-individual variability.
Conclusions:
- A validated, simple kinetic model for human DMSA pharmacokinetics was successfully developed.
- This model holds future potential for predicting blood lead concentrations in patients treated with DMSA.
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