Rapid degradation of disulfiram by serum albumin.

Interaction of disulfiram (DSF, tetraethylthiuram disulfide) with human plasma and albumin was studied by high performance liquid chromatography. Incubation of DSF with plasma resulted in a rapid reduction of the parent drug into diethyldithiocarbamate (DDC). At initial stages of incubation about one half of DDC in the reaction mixture was bound to protein. On further incubation, concentration of protein-bound DDC exceeded the concentration of free DDC. Similar results were obtained when DSF was incubated with bovine serum albumin (BSA) indicating that albumin is the major component of human plasma involved in the reduction of DSF. These data have implications both for the laboratory assay of DSF in human plasma and for the therapeutic use of the drug. When assaying the drug in plasma or serum, DSF standards prepared in protein solution for calibration should take into account the distribution of DSF into the parent drug and its derivatives in a time and protein concentration dependent manner. In a clinical setting, patients with a low serum albumin concentration might require small doses of DSF to achieve an optimal therapeutic effect.