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BAL (2,3-Dimercaptopropanol; dimercaprol) is a metal chelator used clinically in conjunction with edetate calcium disodium (CaNa2EDTA) for lead encephalopathy and severe lead toxicity.22,29 In this instance BAL should precede the first dose of CaNa2EDTA by 4 hours to prevent redistribution of lead to the central nervous system (CNS). Because BAL has a narrow therapeutic index and must be given intramuscularly (IM), succimer is used for patients with less severe lead toxicity. Likewise, the roles of BAL in arsenic and mercury poisoning are being supplanted by succimer and the investigational agent 2,3-dimercaptopropane sulfonate (DMPS), unless the gastrointestinal tract is compromised and IM BAL is indicated.

Investigation into the use of sulfur donors as antidotes was precipitated by the World War II threat of chemical warfare with lewisite (dichloro[2-chlorovinyl]arsine) and mustard gas (dichlorodiethyl sulfide[ClCH2CH2]2S).1,30,31 Both are vesicant gases that cause tissue damage when combined with protein sulfhydryl (SH) groups (Chap. 131).34 The investigations of Stocken and Thompson at Oxford led to the discovery of the dithiol 2,3-dimercaptopropanol, called British anti-Lewisite, which combines with lewisite to form a stable five-membered ring.39,41

BAL has a molecular weight of 124.2 daltons and a specific gravity of 1.21.32Dimercaprol is an oily liquid with only 6% weight/volume water solubility, 5% weight/volume peanut oil solubility, and a disagreeable odor. Aqueous solutions are easily oxidized and therefore unstable. Peanut oil stabilizes BAL and benzyl benzoate (in the ratio of one part BAL to two parts of benzyl benzoate) renders the BAL miscible with peanut oil.35

There are no recent pharmacokinetic studies with BAL. The limited amount of information available dates back to the late 1940s.1,23 Serum concentrations of BAL peak about 30 minutes after IM administration and distribution occurs quickly.35,38 Within 2 hours after IM administration to rabbits, serum concentrations drop quickly. Urinary excretion of BAL metabolites, perhaps partially as glucuronic acid conjugates, accounted for nearly 45% of the dose within 6 hours and 81% of the dose within 24 hours.35,37 Very little is excreted unchanged in the urine.35 BAL is concentrated in the kidney, liver, and small intestine.33 BAL can also be found in the feces, suggesting that enterohepatic circulation exists. Hemodialysis may be useful in removing the BAL—metal chelate in cases of renal failure.22,28,40

Animal Studies

The fear of lewisite attack causing skin lesions, led researchers to investigate the potential for cutaneous application of BAL.39 This was based on its limited water solubility and high lipid solubility. In a rodent model, low concentrations of topical BAL were very effective both in preventing lewisite-induced toxicity and in reversing toxicity when administered within 1 hour of skin exposure.32,34 In rabbits, ocular application of BAL proved effective in preventing eye ...

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