Pharmacokinetics of meso-2,3- dimercaptosuccinic acid in patients with lead poisoning and in healthy adults

Dart, Richard C.; Hurlbut, Katherine M.; Maiorino, Richard M.; Mayersohn, Michael; Aposhian, H. Vasken; Boyer, Leslie V.

doi:10.1016/s0022-3476(94)70217-9

Cited by 43 publications

(39 citation statements)

References 9 publications

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“…Subsequently, we verified the accuracy of our model's predictions by using data from experimental studies, [10,13,17] different from the one used in the parameter optimisation process. [16] One of these studies included lead-poisoned patients (children and adults) and healthy adult volunteers [13] but we used only the data obtained from the healthy volunteers.…”

Section: Model Verification Datamentioning

confidence: 81%

“…Figure 3 shows the calculated and measured plasma and urine DMSA concentrations in three studies. [10,13,17] In the Dart et al [13] study, observed blood DMSA concentrations were provided and had to be converted into plasma DMSA concentrations for comparison purpose (upper panel). Observed DMSA concentrations in plasma were available only in the Maiorino et al [10] study (upper panel).…”

Section: Resultsmentioning

confidence: 99%

“…[13] The data we used for the parameter fitting process as well as for the verification of the model predictions, concerned adults only. Nevertheless, we believe our model could also be used for children treated with DMSA chelation.…”

Section: Discussionmentioning

confidence: 99%

“…[16] One of these studies included lead-poisoned patients (children and adults) and healthy adult volunteers [13] but we used only the data obtained from the healthy volunteers. In these studies, oral DMSA 10 mg/kg body weight was given to healthy volunteers and DMSA blood or plasma concentrations were measured at several time-points.…”

Section: Model Verification Datamentioning

confidence: 99%

“…[9][10][11][12][13] These have shown that after oral administration to healthy adult volunteers, "total" DMSA is distributed in the body's extracellular fluid and in blood. In the latter, total DMSA is almost entirely distributed in the plasma and does not penetrate erythrocytes.…”

Section: Introductionmentioning

confidence: 99%

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Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans

Eijkeren

Olie

Bradberry

et al. 2016

Clinical Toxicology

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Context: 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. Material and 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. ARTICLE HISTORY

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