Abstract
Disulfiram (Antabuse) is one of several aldehyde dehydrogenase (ALDH) inhibitors that raise the plasma level of acetaldehyde following ethanol ingestion. The usually pleasant reaction to ethanol is thereby changed to an unpleasant one, owing to a number of bodily reactions to acetaldehyde. Populations showing genetic polymorphism with a lack of some isozymes of ALDH have exhibited an intolerance to ethanol similar to that seen with disulfiram. A normal isozyme pattern seems to be a prerequisite for the development of alcoholism, which supports the principle of disulfiram treatment. Disulfiram is an irreversible ALDH inhibitor when administered in vivo. Diethylthiomethylcarbamate (Me-DTC) is formed from disulfiram in three metabolic steps. This compound and two further oxidized metabolites appear to be active metabolites of disulfiram. Measurements of plasma Me-DTC or the reduction of leucocyte ALDH 1 activity may be valuable markers for the proper dose titration of disulfiram and the rational use of this drug. Some toxicological points are discussed.
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