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Are we ready to replace dimercaprol (BAL) as an arsenic antidote?

Walther-Straub-Institut für Pharmakologie und Toxikologie, Nuβbaumstrasse 26, D-80336 München, Germany

Bernhard Lieb

Walther-Straub-Institut für Pharmakologie und Toxikologie, Nuβbaumstrasse 26, D-80336 München, Germany

Franz-Xaver Reich

Walther-Straub-Institut für Pharmakologie und Toxikologie, Nuβbaumstrasse 26, D-80336 München, Germany

Göran Hunder

Walther-Straub-Institut für Pharmakologie und Toxikologie, Nuβbaumstrasse 26, D-80336 München, Germany

Udo Walther

Walther-Straub-Institut für Pharmakologie und Toxikologie, Nuβbaumstrasse 26, D-80336 München, Germany

Burckhard Fichtl

Walther-Straub-Institut für Pharmakologie und Toxikologie, Nuβbaumstrasse 26, D-80336 München, Germany

1 Dimercaprol (BAL), 2,3-dimercaptopropanesulpho nate sodium (DMPS) and meso-2,3-dimercaptosucci nic acid (DMSA) are effective arsenic antidotes, but the question which one is preferable for optimal therapy of arsenic poisoning is still open to discussion. Major drawbacks of BAL include (a) its low therapeutic index, (b) its tendency to redistribute arsenic to brain and testes, for example, (c) the need for (painful) intramuscular injection and (d) its unpleasant odour.

2 The newer antidotes DMPS and DMSA feature low toxicity and high therapeutic index. They can be given orally or intravenously due to their high water solubility. While these advantages make it likely that DMPS and DMSA will replace BAL for the treatment of chronic arsenic poisoning, acute intoxication - espe cially with lipophilic organoarsenicals - may pose a problem for the hydrophilic antidotes, because their ionic nature can adversely affect intracellular avail ability.

3 This article focuses on aspects dealing with the power of BAL, DMPS, and DMSA to mobilize tissue-bound arsenic in various experimental models, such as monolayers of MDCK (=Madin-Darby canine kidney) cells from dog kidney, isolated perfused liver from guinea-pigs, and perfused jejunal segments from rat small intestine.

4 The results show that hydrophilic DMPS and DMSA may fail to rapidly and completely remove arsenic that has escaped from the extracellular space across tight epithelial barriers. However, owing to their low toxicity, which allows larger doses to be applied, and the potential modification of their pharmacokinetics by means of inert oral anion-exchange resins, DMPS and DMSA may advantageously replace BAL when ever intervention time is not critical. With severe intoxication by organic arsenicals, when the point-of- no-return is a limiting factor, BAL may still have a place as an arsenic antidote.

Key Words: arsenicals • antidotes • in vitro models • cell culture • perfused organs • therapy

Human & Experimental Toxicology, Vol. 16, No. 8, 460-465 (1997)
DOI: 10.1177/096032719701600807


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