COMPARATIVE-STUDIES ON THE PHARMACOKINETICS OF HYDROPHILIC PROLINEDITHIOCARBAMATE, SARCOSINEDITHIOCARBAMATE AND THE LESS HYDROPHILIC DIETHYLDITHIOCARBAMATE

The pharmacokinetics of the antitoxic and anticarcinogenic compounds diethyldithiocarbamate, prolinedithiocarbamate and sarcosinedithiocarbamate were compared in rats. The bioavailability, the distribution in the organism, the oxidation to thiuramdisulfides, the cleavage to CS2 and the excretion in urine and bile were investigated. The results showed different behaviour of the three compounds. The more toxic diethyldithiocarbamate had a short in vivo half-life, was oxidized to tetraethylthiuramdisulfide in blood, and was metabolized to high yields of CS2 in 24 h. In contrast, prolinedithiocarbamate was more stable in vivo, was found predominantly in the urinary tract and was excreted in urine. The differences could not be explained by the presence of the carboxy group in the latter dithiocarbamate, since sarcosinedithiocarbamate, which also contains a carboxy group, behaved like diethyldithiocarbamate.