Sodium-2,3-Dimercaptopropaneslilfonate: Pharmacokinetic Data and Therapy of Mercury Poisoning
The water-soluble derivative of BAL, Sodium-2,3-dimercaptapropanesulfonate (DMPS) has shown very good results in improving the urinary elimination of Hg in cases of poisoning with inorganic as well as with organic Hg compounds (B. Gabard, Arch. Toxicol., 35, 15, 1976 and Toxicol. Appl. Pharmacol., 38, 415, 1976). For the first time, pharmacokinetic data were obtained in the rat using 1,3-14C-labeled DMPS. Over a wide dose range (0.1–1.0 mmol/kg), the distribution does not depend on the dose. The highest concentrations are found immediately after injection in the kidneys (7.4±0.04% of the dose/g wet weight) and in plasma (2.3±0.02%/ml), the lowest in the brain (0.06±0.04%/g). The excretion is very rapid (T1/2 = 19 min) and follows a monoexponential curve in plasma and in most of the organs during the first hour after the injection. 80–90% of the dose are excreted within the first 6 hours. The plasma clearance of DMPS equals the glomerular filtration rate of the rat as measured under steady-state conditions. The apparent volume of distribution of the radioactivity after an i.v. injection is equivalent to the volume of the extracellular water. After oral administration 30–40% are absorbed from the gut. The results of the pharmacokinetic analysis raise the question how an intracellularly deposited metal is removed by an extracellular chelating agent. Furthermore, they explain the lack of side-effects during treatment of heavy-metal poisoning with DMPS and make the drug especially suited for chronic poisoning cases.