FATE AND DISTRIBUTION OF [C-14] -(N,N-DIETHYLDITHIOCARBAMOYL)-N-ACETYL-L-CYSTEINE, AN ANTIMUTAGENIC MIXED DISULFIDE FROM DISULFIRAM, IN RATS

S-(N,N-Diethyldithiocarbamoyl)-N-acetyl-L-cysteine (AC-DDTC) is a mixe d disulfide from disulfiram and N-acetyl-L-cysteine, which possesses p utative anticarcinogenic and antimutagenic properties. The present stu dy describes the absorption, distribution, metabolism and excretion of C-14-labeled AC-DDTC in rats AC-DDTC was well absorbed after oral adm inistration. Based on the excretion of radioactivity in urine, the min imum absorption was about 73%. The rate of absorption was very rapid, with the peak level of radioactivity in plasma after 15 min of adminis tration. Mean C-max value for N,N-diethyldithiocarbamate (DDTC) after oral dose of AC-DDTC (20 mg/kg) was 3.8 +/- 0.2 nmol/ml at 15 min and the mean residence time was 47.1 +/- 2.8 min. After oral administratio n of [C-14]AC-DDTC, radioactivity was distributed relatively rapidly. Maximum concentrations were observed in the liver (0.443% dose/g), kid neys (0.496% dose/g), oesophagus (0.313% dose/g) and in the adrenals ( 0.364% dose/g) at 30 min to 1 h after dosing. Liver was the only organ which contains a considerable amount of radioactivity (0.091% dose/g) 24 h after dosing. Two metabolites of AC-DDTC following oral administ ration were identified in the plasma and liver by GC and HPLC using ex tractive alkylation technique, namely DDTC and its methyl ester. Urina ry excretion, was a major route of elimination of radioactivity derive d from [C-14]AC-DDTC, in that about 73% of the dose was recovered in u rine whereas only 14% was found in feces over 7 days.