Urinary excretion of meso-2,3-dimercaptosuccinic acid in human subjects

Abstract

The urinary excretion of meso-2,3-dimercaptosuccinic acid (DMSA), which is an effective chelating agent for lead, was determined after the oral administration of 10 mg DMSA/kg to six normal young men. The DMSA that was absorbed was extensively biotransformed. After 14 hours only 2.53% of the administered DMSA was excreted in the urine as unaltered DMSA and 18.1% as altered forms. The unaltered DMSA was 12% of the total DMSA found in the urine. The altered form(s) of DMSA was 88% of the total urinary DMSA. The altered DMSA can be converted to unaltered DMSA by electrolytic reduction, which indicates that the altered forms of DMSA are disulfides. The excretion of altered DMSA reached a peak between 2 and 4 hours after DMSA administration. There were small but statistically significant increases in the excretion of zinc, copper, and lead after DMSA administration. DMSA did not influence the urinary excretion of 27 other metals and elements.

Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans

“…Observed DMSA concentrations in plasma were available only in the Maiorino et al [10] study (upper panel). Observed urine data were reported only in the Aposhian et al [17] and Maiorino et al [10] studies (lower panel). As the predicted values were calculated for the same DMSA dose (oral administration of 10 mg/kg DMSA) and standard weight, both predicted curves of the upper panel are similar.…”

“…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).…”

“…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.…”

“…As an additional parameter, the distribution volume (L/kg body weight) should be known to relate the amount of systemic DMSA to its plasma concentration. Information found in another study [17] permitted us to reduce the number of unknown parameters from 5 to only 3: the total elimination rate from the gut k g ¼ k a þk f , the total elimination rate from the system k s ¼ k b þk u , and the volume of distribution V D . This parameter reduction is based on the fact that the relative excretion of DMSA in urine is assumed to be approximately 20% after oral administration and 81% after intravenous administration.…”

“…This parameter reduction is based on the fact that the relative excretion of DMSA in urine is assumed to be approximately 20% after oral administration and 81% after intravenous administration. [17] We have assumed the latter percentage to be 80%, for convenience. Detailed equations can be found in the Appendix.…”