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  1. Pharmacology. Unithiol (DMPS; 2,3-dimercaptopropanol-sulfonic acid), a dimercapto chelating agent that is a water-soluble analog of BAL, is used in the treatment of poisoning by several heavy metals, principally mercury, arsenic, and lead. Available on the official formularies of Russia and former Soviet countries since 1958 and in Germany since 1976, unithiol has been legally available from compounding pharmacists in the United States since 1999. The drug can be administered orally and parenterally. Oral bioavailability is approximately 50%, with peak blood concentrations occurring in approximately 3.7 hours. It is bound extensively to plasma proteins, mainly albumin. More than 80% of an intravenous dose is excreted in the urine, 10% as unaltered unithiol, and 90% as transformed products, predominantly cyclic DMPS sulfides. The elimination half-life for total unithiol is approximately 20 hours. Unithiol and/or its in vivo biotransformation products form complexes with a variety of inorganic and organic metal compounds, increasing excretion of the metal in the urine and decreasing its concentration in various organs, particularly the kidneys. Renal elimination of the metal chelates appears to be mediated in part by the multidrug resistance protein 2 (Mrp2). Unlike BAL, unithiol does not redistribute mercury to the brain.

  2. Indications

    1. Unithiol has been used primarily in the treatment of intoxication by mercury, arsenic, and lead. In animal models, unithiol has averted or reduced the acute toxic effects of inorganic mercury salts and inorganic arsenic when administered promptly (minutes to hours) after exposure. Unithiol is associated with a reduction in tissue levels of mercury, arsenic, and lead in experimental animals, and it increases the excretion of those metals in humans. However, randomized, double-blind, placebo-controlled clinical trials demonstrating therapeutic efficacy in acute or chronic heavy metal poisoning have not been reported.

    2. Animal studies and a few case reports suggest that unithiol may have utility in the treatment of poisoning by bismuth compounds. Animal studies suggest that unithiol may increase survival after acute exposure to polonium 210; however, redistribution to the kidneys may occur.

  3. Contraindications

    1. History of allergy to the drug.

    2. Because renal excretion is the predominant route of elimination of unithiol and its metal complexes, caution is warranted in administering unithiol to patients with severe renal insufficiency. Published reports support the use of unithiol as an adjunct to high flux hemodialysis or hemodiafiltration in patients with anuric renal failure caused by mercury salts and bismuth.

  4. Adverse effects

    1. The German manufacturer (Heyl) notes a low overall incidence (<4%) of adverse side effects.

    2. Self-limited, reversible allergic dermatologic reactions such as exanthems and urticaria have been the most commonly reported adverse effect. Isolated cases of major allergic reactions, including erythema multiforme and Stevens-Johnson syndrome, have been reported.

    3. Because rapid intravenous administration may be associated with vasodilation and transient hypotension, intravenous injections of unithiol should be administered slowly, over a 15- to 20-minute interval.

    4. Unithiol increases the urinary excretion of copper and zinc, an effect that is not anticipated to be clinically significant in standard courses of treatment ...

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