Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans

Abstract

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

Dimercaptosuccinic acid in combination with carbapenems against isogenic strains of Escherichia coli producing or not producing a metallo-β-lactamase in vitro and in murine peritonitis

“…Pharmacokinetic data in humans concerning DMSA are scarce, but available studies indicate mean peak plasma concentrations of about 20-50 lM after a standard 10 mg/kg oral dose (Table S3). 16,39,40 These concentrations are comparable to those obtained in mice with 200 mg/kg, the dose that demonstrated a beneficial effect in combination with imipenem in vivo. Thus, an in vivo benefit was obtained with plasma concentrations comparable to those achieved in humans with the standard oral dose of DMSA of 10 mg/kg.…”