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Chapter: Basic & Clinical Pharmacology : Heavy Metal Intoxication & Chelators

Unithiol (Dimercaptopropanesulfonic Acid, DMPS)

Unithiol, a dimercapto chelating agent that is a water-soluble analog of dimercaprol, has been available in the official formularies of Russia and other former Soviet countries since 1958 and in Germany since 1976.

UNITHIOL (DIMERCAPTOPROPANESULFONIC ACID, DMPS)

Unithiol, a dimercapto chelating agent that is a water-soluble analog of dimercaprol, has been available in the official formularies of Russia and other former Soviet countries since 1958 and in Germany since 1976. It has been legally available from com-pounding pharmacies in the USA since 1999. Unithiol can be administered orally and intravenously. Bioavailability by the oral route is approximately 50%, with peak blood levels occurring in approximately 3.7 hours. Over 80% of an intravenous dose is excreted in the urine, mainly as cyclic DMPS sulfides. The elimi-nation half-time of total unithiol (parent drug and its transforma-tion products) is approximately 20 hours. Unithiol exhibits protective effects against the toxic action of mercury and arsenic in animal models, and it increases the excretion of mercury, arse-nic, and lead in humans. Animal studies and a few case reports suggest that unithiol may also have usefulness in the treatment of poisoning by bismuth compounds.


Indications & Toxicity

Unithiol has no FDA-approved indications, but experimental studies and its pharmacologic and pharmacodynamic profile suggest that intravenous unithiol offers advantages over intra-muscular dimercaprol or oral succimer in the initial treatment of severe acute poisoning by inorganic mercury or arsenic. Aqueous preparations of unithiol (usually 50 mg/mL in sterile water) can be administered at a dosage of 3–5 mg/kg every 4 hours by slow intravenous infusion over 20 minutes. If a few days of treatment are accompanied by stabilization of the patient’s cardiovascular and gastrointestinal status, it may be possible to change to oral administration of 4–8 mg/kg every 6–8 hours. Oral unithiol may also be considered as an alterna-tive to oral succimer in the treatment of lead intoxication.

Unithiol has been reported to have a low overall incidence of adverse effects (< 4%). Self-limited dermatologic reactions (drug exanthems or urticaria) are the most commonly reported adverse effects, although isolated cases of major allergic reactions, includ-ing erythema multiforme and Stevens-Johnson syndrome, have been reported. Because rapid intravenous infusion may cause vasodilation and hypotension, unithiol should be infused slowly over an interval of 15–20 minutes.


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