Determination and metabolism of dithiol chelating agents. XII. Metabolism and pharmacokinetics of sodium 2,3-dimercaptopropane-1-sulfonate in humans.

The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS) is used p.o. for the treatment of chronic lead and Hg intoxication in humans. The metabolism and pharmacokinetics of DMPS were determined after p.o. administration of 300 mg of DMPS to each of 10 normal young men. The absorbed DMPS was metabolized rapidly and extensively to a disulfide form(s). By 24 hr after DMPS administration, the area under the blood concentration-time curve of unaltered DMPS was 3.9 compared to 143 for altered DMPS. Altered DMPS is the difference between total DMPS and unaltered DMPS. Unaltered DMPS is the unbound, parent compound;, total DMPS consists of unaltered DMPS plus oxidized [disulfide] DMPS which is determined after reduction with dithiothreitol. In blood the altered form was confined to plasma. By 15 hr, only 3.7% of the administered DMPS was excreted in the urine as unaltered DMPS and 38.7% as altered DMPS. The unaltered and altered DMPS represented 9 and 91%, respectively, of the total amount of DMPS in the urine. Altered DMPS was converted to unaltered DMPS by treatment with dithiothreitol, which indicates that the altered DMPS is a disulfide(s). There was a high correlation between the urinary excretion of Hg and the urinary excretion of unaltered DMPS (r = 0.920 +/- 0.022 S.E.).