Elimination kinetics of disulfiram in alcoholics after single and repeated doses

Abstract

Disulfiram elmination kinetics were determined in 15 male alcoholics after 250 mg disulfiram taken orally as a single dose and again after 12 dosing days. Apparent t1/2 [half lives] were calculated for disulfiram, diethyldithiocarbamate (DDTC), diethyldithiocarbamate-methyl ester (DDTC-Me), diethylamine (DEA) and carbon disulfide (CS2) and were found to be 7.3, 15.5, 22.1, 13.9 and 8.9 h, respectively. Elimination t1/2 for CS2 in breath was 13.3 h. Average time to reach maximal plasma concentration after either single or repeated doses was 8-10 h for disulfiram, DDTC, DDTC-Me, DEA and CS2 in breath, while plasma CS2 concentration peaked 5-6 h after disulfiram. After single and repeated dosing 22.4 and 31.3% of the disulfiram was eliminated in the breath during 1 dosing interval. In urine, 1.7% and 8.3% of the disulfiram dose was eliminated as DDTC-glucuronide after single and repeated dosing, while DEA accounted for 1.6% and 5.7% of the dose. There was marked intersubject variability in plasma levels of disulfiram and its metabolites. This variability may be the result of disulfiram lipid solubility, differences in plasma protein binding, or the effect of enterohepatic cycling.