Succimer toxicity

Laughlin NK Harlow Primate Laboratory, Madison, Wl Effect of succimer therapy on lead-induced neurobehavioral and organ system toxicity (rhesus monkey) National Institute of Environmental Health Sciences... 

Laughlin NK University of Wisconsin, Madison, Wl Determine the efficacy of succimer chelation in alleviating lead toxicity in rhesus monkeys evaluate the redistribution of lead from endogenous sources in response to chelation National Center For Research Resources... 

Succimer is currently FDA-approved for the treatment of children with blood lead concentrations greater than 45 wg/dL, but it is also commonly used in adults. The usual dosage is 10 mg/kg orally three times a day. Oral administration of succimer is comparable to parenteral EDTA in reducing blood lead concentration and has supplanted EDTA in outpatient treatment of patients capable of absorbing the oral drug. However, despite the demonstrated capacity of both succimer and EDTA to enhance lead elimination, their value in reversing established lead toxicity or in otherwise improving therapeutic outcome has yet to be established by a placebo-controlled clinical trial. 

In a UK study, single oral doses of dimercaptopropane sulfonic acid or succimer in different combinations with or without acetylcysteine and potassium citrate were given to 191 patients considered to have mercury toxicity from amalgam dental fillings (2). After a single dose, about 5% of patients complained of mild gastrointestinal discomfort, fatigue, mental fuzziness, headache, and diuresis. These usually cleared within 6 hours of the dose and were considered to be due to heavy metal mobilization. There were no cases of hypersensitivity. 

Succimer is the meso isomer of 2,3-dimethylmercapto-succinic acid (DMSA). It is used as a lead chelator for oral administration (1). Nausea, vomiting, diarrhea, and anorexia are common. Rashes, sometimes necessitating withdrawal, have been reported in up to 10% of adults and 5% of children, and mild transient rises in serum transaminase activity in 6-10% (mostly adults) (2,3). Life-threatening hyperthermia occurred on two occasions in one subject, but no details were given. Iron can be safely and effectively given to patients taking succimer, which (unlike dimercaprol) does not appear to deplete iron stores or to form a toxic chelate that would preclude the parenteral administration of iron (3). 

Dimercaprol (BAL) Arsenic, gold, mercury, lead oral succimer for milder lead and mercury toxicity... 

Toxicity with succimer is less than that with dimercaprol perhaps because its relatively lower lipid solubility minimizes... 

Femal Peptinimid Petinimid Petnidar Pyknotepsinum Simatin Succimal Suxilep Suximal Suxinutin Thllopemal Zarontin. C NOy mol wt 141.17. C 59.55%, H 7.85%, N 9.92%, O 22.67%. Prepn Sircar, J. Chem. Soc. 1927, 1252. Comparative clinical trial with valproic acid, q.v., ia epilepsy S. Sato el aL. Neurology 32, 157 (1982). Acute toxicity data H. Najer et al.. Bull. Soc. Chim. France 3, 1119 (1966). Brief review S. J. Wallace, Neurol. Clin. 4,601 (1986). 

Toxicity with succimer is less than that with dimercaprol, perhaps because its relatively lower lipid solubility minimizes its uptake into cells. Nonetheless, transient elevations in hepatic transaminases are observed following treatment with succimer. The most commonly reported adverse effects of succimer treatment are nausea, vomiting, diarrhea, and loss of appetite. Rashes also have been reported that may necessitate discontinuation of therapy. 

Clinical use Succimer is used for the oral treatment of lead toxicity in children and adults, and it is as effective as parenteral EDTA in reducing blood lead concentration. Succimer is effective in arsenic and mercury poisoning, if given within a few hours of exposure. 

Toxicity While succimer appears to be less toxic than dimercaprol, gastrointestinal distress, CNS effects, skin rash, and elevation of liver enzymes may occur. 

The treatment of choice in acute arsenic poisoning is intramuscular dimercaprol. While succimer is less toxic than dimercaprol, it is available only in an oral formulation and its absorption may be impaired due to the severe gastroenteritis that occurs in acute poisoning with arsenic. The answer is (B). 

III. 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 hemodialysis clearance of toxic metals in anuric patients. 

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