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  1. Pharmacology

    1. Succimer (meso-2,3-dimercaptosuccinic acid [DMSA]) is a chelating agent that is used in the treatment of intoxication from several heavy metals. A water-soluble analog of BAL (dimercaprol), succimer enhances the urinary excretion of lead and mercury. Its effect on the elimination of the endogenous minerals calcium, iron, and magnesium is insignificant. Minor increases in zinc and copper excretion may occur. In an animal model, oral succimer was not associated with a significant increase in the GI absorption of lead or inorganic mercury (as mercuric chloride); the effect of oral succimer on the GI absorption of arsenic is not known.

    2. After oral administration, peak blood concentrations occur in approximately 3 hours. Distribution is predominantly extracellular, and in the blood, succimer is extensively bound (>90%) to plasma proteins. Succimer is eliminated primarily in the urine, where 80-90% appears as mixed disulfides, mainly 2:1 or 1:1 cysteine-succimer adducts. Studies suggest that these adducts, rather than the parent drug, may be responsible for metal-chelating activity in vivo. Renal elimination of the metal chelates appears to be mediated in part by the multidrug resistance protein 2 (Mrp2). The elimination half-life of transformed succimer is approximately 2–4 hours. Renal clearance may be diminished in the setting of pediatric lead intoxication.

  2. Indications

    1. Succimer is approved for the treatment of lead intoxication, where it is associated with increased urinary excretion of the metal and concurrent reversal of metal-induced enzyme inhibition. At moderately elevated blood lead concentrations, oral succimer is comparable with parenteral calcium EDTA in decreasing blood lead concentrations. The efficiency of succimer in eliminating lead from the blood and tissues may somewhat decline at very high blood concentrations of lead (eg, >100 mcg/dL). Although succimer treatment has been associated with subjective clinical improvement, controlled clinical trials demonstrating therapeutic efficacy have not been reported. A large, randomized, double-blind placebo-controlled trial of succimer in children with blood lead concentrations between 25 and 44 mcg/dL found no evidence of benefit in clinical outcome or long-term blood lead reduction.

    2. Succimer is protective against the acute lethal and nephrotoxic effects of mercuric salts in animal models and increases urinary mercury excretion in animals and humans. It, therefore, may have clinical utility in the treatment of human poisoning by inorganic mercury. In a recent animal model of methylmercury exposure during pregnancy, succimer was effective in reducing the maternal and fetal mercury burden; however, unithiol appeared to be somewhat more potent in that setting.

    3. Succimer is protective against the acute lethal effects of arsenic in animal models and may have potential utility in acute human arsenic poisoning.

  3. Contraindications. History of allergy to the drug. Because succimer and its transformation products undergo renal elimination, safety and efficacy in patients with severe renal insufficiency are uncertain. There is no available evidence that succimer increases the hemodialysis clearance of toxic metals in patients with anuria.

  4. Adverse effects

    1. Gastrointestinal disturbances including anorexia, nausea, vomiting, and diarrhea are the most common side effects and occur in ...

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