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

<b>Context:</b> 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. <b>Materials and methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> Our model is able to predict blood lead concentrations after succimer therapy, at least, in situations where the duration of lead exposure is known.

<b>研究背景：</b>动力学模型可在临床医师处理铅中毒病例时提供辅助。目前已有多款可模拟铅代谢动力学的模型，但尚无一款能够预测螯合疗法对铅中毒的疗效。本研究旨在构建一款模型，用于预测二巯基丁二酸（succimer, dimercaptosuccinic acid; DMSA）螯合疗法对血铅浓度的影响。
<b>材料与方法：</b>本研究将二室动力学二巯基丁二酸模型整合入已有的生理药代动力学（Physiologically Based Pharmacokinetic, PBPK）铅模型中，构建了螯合铅治疗（Chelation Lead Therapy, CLT）模型。通过模拟铅中毒且接受二巯基丁二酸治疗患者的临床观测数据，对该模型的预测准确性进行了评估。CLT模型将血铅浓度计算为背景暴露与急/慢性铅中毒所致血铅水平之和，后者（即急/慢性铅中毒）的病因包括摄入含铅传统药物，或职业性暴露于铅污染的环境空气。研究中已知患者的铅暴露时长，将CLT模型预测的血铅浓度与实测血铅浓度进行了对比。
<b>结果：</b>螯合治疗前患者的血铅浓度范围为99~150 μg/dL。该模型可准确模拟二巯基丁二酸治疗期间及治疗后的血铅浓度变化。部分患者的尿铅排泄模式被成功预测，而其余患者的预测效果欠佳。
<b>结论：</b>本研究所构建的模型可预测二巯基丁二酸治疗后的血铅浓度，至少在铅暴露时长已知的场景中可行。