Fate and distribution of [14C]S-(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 mixed disulfide from disulfiram and N-acetyl-L-cysteine, which possesses putative anticarcinogenic and antimutagenic properties. The present study describes the absorption, distribution, metabolism and excretion of 14C-labeled AC-DDTC in rats. AC-DDTC was well absorbed after oral administration. Based on the excretion of radioactivity in urine, the minimum absorption was about 73%. The rate of absorption was very rapid, with the peak level of radioactivity in plasma after 15 min of administration. Mean Cmax 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 administration of [14C]AC-DDTC, radioactivity was distributed relatively rapidly. Maximum concentrations were observed in the liver (0.443% dose/g), kidneys (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 administration were identified in the plasma and liver by GC and HPLC using extractive alkylation technique, namely DDTC and its methyl ester. Urinary excretion was a major route of elimination of radioactivity derived from [14C]AC-DDTC, in that about 73% of the dose was recovered in urine whereas only 14% was found in feces over 7 days.
Lee
B H
BH
Doping Control Center, Korea Institute of Science and Technology, Seoul, Korea.
Ryu
J C
JC
Park
J
J
Bertram
B
B
Wiessler
M
M
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D016587:Antimutagenic Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D001711:Biotransformation; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004221:Disulfiram / Q000031:analogs & derivatives*; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D016587:Antimutagenic Agents; C098444:S-(N,N-diethyldithiocarbamoyl)-N-acetylcysteine; D004221:Disulfiram; D000111:Acetylcysteine