Distribution of Disulfiram and Its Chief Metabolites over Erythrocyte Cell Membranes and Inactivation of Erythrocyte Aldehyde Dehydrogenase Activity

Abstract

The distribution of disulfiram (Antabuse over erythrocyte cell membranes and the inhibitory action of the parent drug and its metabolites on a disulfiram sensitive erythrocyte isozyme of aldehyde dehydrogenase (ALDH) was investigated in intact and haemolyzed human erythrocytes. These studies showed that not only disulfiram but also its bis(diethyldithiocarbamato) copper complex (Cu(DDC)2) were distributed over the erythrocyte cell membranes. In addition, disulfiram was the only substance examined that inactivaed erythrocyte ALDH, a reaction which was dependent on the concentration of disulfiram added.

Plasma protein binding of disulfiram and its metabolite diethylthiocarbamic acid methyl ester

“…Albumin is the only binding protein of both [i4C]disulfiram and [I4C]Me-DTC, as shown by the single band of radiolabelled albumin that separated from other plasma proteins on an agarose electrophoretic gel. In the blood of patients on disulfiram treatment or in fresh blood to which disulfiram had been added, the drug was rapidly reduced to the monomer diethyldithiocarbamic acid and further converted to its bis(diethy1dithiocarbamato) copper complex (Johansson & Stankiewicz 1985;Johansson 1990). Before quantitative determination of disulfiram concentrations in plasma could be obtained, it was essential to add stabilizing agents to the blood collection tubes promptly at the time of collection or at preparation when disulfiram was added to fresh blood or plasma in-vitro.…”