British anti-Lewisite (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.23,30 In this, BAL should precede the first dose of CaNa2EDTA by 4 hours to prevent redistribution of lead to the central nervous system (CNS). BAL has a narrow therapeutic index, BAL must be administered intramuscularly (IM) because it is formulated in peanut oil. Oral succimer is used for patients with less severe lead toxicity. The roles for BAL in arsenic and mercury poisoning have diminished since the development of succimer and the investigational chelator 2,3-dimercaptopropane sulfonate (DMPS). BAL is still indicated when the gastrointestinal tract is compromised.
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).1,31,32 Both are vesicants that cause tissue damage when combined with protein sulfhydryl groups (Chap. 132).35 The investigations of Stocken and Thompson at Oxford led to the discovery of the dithiol 2,3-dimercaptopropanol (or BAL) that combines with lewisite to form a stable five-membered ring.40,42
BAL has a molecular weight of 124.2 Da and a specific gravity of 1.21.33 It 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 in peanut oil.36
The sulfhydryl groups of dimercaprol form chelates with certain metals, which are then excreted in the urine. Lead, arsenic, and inorganic mercury salts are the metals most amenable to chelation with BAL.
There are no recent studies of the pharmacokinetics of BAL. The limited information available was first described in the late 1940s.1,24 Serum concentrations of BAL peak about 30 minutes after IM administration, and distribution occurs rapidly.36,39 Within 2 hours after IM administration to rabbits, serum concentrations rapidly fall. 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.36,38 Very little is excreted unchanged in the urine.36 BAL is concentrated in the kidney, liver, and small intestine.34 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 kidney failure.23,29,41